We thank Dr. John Greaves and Ms. Soroosh Sorooshian, Department of Chemistry, University of California, Irvine Mass Spectrometry Facility, for mass spectrometric analyses. We also thank Mr. Jacob Buchanan for helpful discussions, as well as Miss Stephanie J. Conn, Mrs. Shannon M. Huffman (Vreeland), and Miss Alexandra N. Wexler for early stage work on this project. Partial funding was provided by the Central Washington University (CWU) School of Graduate Studies (C.E.M), the CWU Seed Grant Program, and the CWU Faculty Research Program.

<ol>
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The authors have nothing to declare.

מאמצים ראשוניים להכין clavatadine גייס גישה מסורתית, עקיפת guanidinylation מ מבשר אמין מתאים, אשר במקרה זה היה יזיד סופנית. בלב המאמץ הזה היה האיחוד של שני החצאים של המולקולה לבנות מחצית carbamate. למרבה הצער, כל הניסיונות לממש הפחתה תזיד בציפיית guanidinylation בשלב מאוחר מתוכנן לא צלחו. 25...

המטרה של הווידאו הזה היא להראות כיצד בשיטת guanidinylation ישירה והתחילה לעשות מבנה guanidine מסוף הוא מעשית יותר, מהיר, ויעיל יותר מאשר שיטות מסורתיות guanidinylation בסינתזה אורגנית. הקבוצה guanidine פונקציונלי, נמצא על ארגינין חומצה אמינית, היא אלמנט מבני מפתח מוצרים רבים ותרופות טבע מורכבים. התגלית ועיצוב guanidine חדשה המכילה מוצרים טבעיים ומולקולות קטנות להקים את צורך שיטת guanidinylation יעילה יותר. הגישה העוקפת הנפוצה כולל ההקדמה של מבשר guanidine סמוי כי הוא חשף בשלב מאוחר בסינתזה. לעומת זאת, טקטיקה פשוטה מתקינה guanidine מוגן על גבי אמין עיקרי מוקדם מסלול סינטטי. אופי תגובתי של guanidines בדרך כלל מונע מהם שימוש שגרתי ללא אסטרטגיה קבוצת הגנה מתאימה. באופן מסורתי, שיטותקבוצה להוסיף guanidine תפקודית כללה גישה עקיפה שכלל צעדי הגנה מרובים ואחריו הוספת guanidine בסוף הסינתזה. שני סינתזות האחרונות ממחישות את החסרונות הגלומים 1,2 guanidinylation עקיף. השיטה ישיר דיווחה בזאת כרוכה להגיב ריאגנט guanidine מוגן עם אמין ראשוני בשלב המוקדם של הסינתזה של מולקולת נתונה ולאחר מכן deprotecting אותו בסוף של הסינתזה. אסטרטגיה זו נפרסה בהצלחה בסינתזה כוללת האחרונה של אלקלואידים ימיים פעילים ביולוגי clavatadine A A ו phidianidine ו- B 3,4. אמנם שיטת guanidinylation ישירה זה יש יתרונות על פני שיטות מסורתיות של guanidinylation זה עדיין יש חסרונות. התנאים הכימיים כי guanidine המוגן יכול לשרוד יהיה תלוי בקבוצה להגן מועסקים. למרות החסרונות הפוטנציאליים הללו, שיטת guanidinylation הישירה היא אסטרטגיה המאפשרתלהוסיף guanidines מסוף אמין ראשונית לשימוש בסינתזה של מולקולות אורגניות מורכבות.

<table><tbody><tr><td>Chloroform-d</td><td>Sigma-Aldrich</td><td>612200-100G</td><td>99.8% D, 0.05% v/v tetramethylsilane; Caution: toxic</td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td></td><td>185965-50G</td><td>99.9% D, 1% v/v tetramethylsilane</td></tr><tr><td>sodium thiosulfate pentahydrate</td><td>Sigma-Aldrich</td><td>S8503-2.5KG</td><td></td></tr><tr><td>sodium sulfate, anhydrous</td><td>Sigma-Aldrich</td><td>238597-2.5KG</td><td></td></tr><tr><td>silica gel</td><td>Fisher Scientific</td><td>S825-25</td><td>Merck, Grade 60, 230-400 mesh</td></tr><tr><td>washed sea sand</td><td>Sigma-Aldrich</td><td>274739-5KG</td><td></td></tr><tr><td>hexane</td><td>Sigma-Aldrich</td><td>178918-20L</td><td>Caution: flammable</td></tr><tr><td>ethyl acetate</td><td>Sigma-Aldrich</td><td>319902-4L</td><td></td></tr><tr><td>methylene chloride</td><td>Sigma-Aldrich</td><td>D65100-4L</td><td></td></tr><tr><td>sodium chloride</td><td>Sigma-Aldrich</td><td>S9888-10KG</td><td></td></tr><tr><td>sodium bicarbonate</td><td>Sigma-Aldrich</td><td>S6014-2.5KG</td><td></td></tr><tr><td>acetic acid</td><td>Sigma-Aldrich</td><td>695092-2.5L</td><td></td></tr><tr><td>hydrochloric acid</td><td>Sigma-Aldrich</td><td>258248-2.5L</td><td>Caution: Corrosive</td></tr><tr><td>bromine</td><td>Sigma-Aldrich</td><td>470864-50G</td><td>&gt;99.99% trace metals basis; Caution: Corrosive, causes severe burns</td></tr><tr><td>hydrobromic acid</td><td>Sigma-Aldrich</td><td>244260-500ML</td><td>48% aqueous; Caution: Corrosive</td></tr><tr><td>2,5-dimethoxyphenylacetic acid</td><td>ChemImpex</td><td>26909</td><td></td></tr><tr><td>chloroform</td><td>Sigma-Aldrich</td><td>132950-4L</td><td>Caution: Toxic</td></tr><tr><td>tetrahydrofuran</td><td>Sigma-Aldrich</td><td>360589-4x4L</td><td>Caution: highly flammable</td></tr><tr><td>&lt;em&gt;N,N&lt;/em&gt;-diisopropylethylamine</td><td>Sigma-Aldrich</td><td>D125806-500ML</td><td>Caution: Corrosive</td></tr><tr><td>triethylamine</td><td>Sigma-Aldrich</td><td>T0886-1L</td><td>Caution: Corrosive</td></tr><tr><td>3 Angstrom molecular sieves</td><td>Sigma-Aldrich</td><td>208574-1KG</td><td></td></tr><tr><td>calcium hydride</td><td>Sigma-Aldrich</td><td>213268-100G</td><td>Caution: Corrosive, reacts violently with water</td></tr><tr><td>ammonium molybdate</td><td>Sigma-Aldrich</td><td>431346-50G</td><td></td></tr><tr><td>phosphomolybdic acid</td><td>Sigma-Aldrich</td><td>221856-100G</td><td></td></tr><tr><td>cerium(IV) sulfate</td><td>Sigma-Aldrich</td><td>359009-25G</td><td></td></tr><tr><td>1-butanol</td><td>Sigma-Aldrich</td><td>537993-1L</td><td></td></tr><tr><td>1,4-butanediamine</td><td>Sigma-Aldrich</td><td>D13208-100G</td><td>Caution: Corrosive / warm in hot water bath to melt prior to use</td></tr><tr><td>triphosgene</td><td>VWR</td><td>200015-064</td><td>Caution: Highly Toxic</td></tr><tr><td>methanol</td><td>Sigma-Aldrich</td><td>646377-4X4L</td><td></td></tr><tr><td>sodium acetate</td><td>Sigma-Aldrich</td><td>241245-100G</td><td></td></tr><tr><td>Dimethylsulfoxide-d&lt;sub&gt;6&lt;/sub&gt;</td><td>Sigma-Aldrich</td><td>570672-50G</td><td>Anhydrous, 99.9% D</td></tr><tr><td>sodium hydroxide</td><td>Sigma-Aldrich</td><td>221465-500G</td><td>Caution: Corrosive</td></tr><tr><td>guanidine hydrochloride</td><td>Sigma-Aldrich</td><td>G4505-25G</td><td>Caution: Toxic, Corrosive</td></tr><tr><td>di-tert-butyl dicarbonate</td><td>VWR</td><td>200002-018%</td><td>Caution: Toxic / may warm in hot water bath to melt prior to use</td></tr><tr><td>trifluoromethanesulfonic anhydride</td><td>Fisher Scientific</td><td>50-206-771</td><td>98%, anhydrous; Caution: toxic, corrosive, extremely moisture sensitive</td></tr></tbody></table>

a direct, early stage guanidinylation protocol for the synthesis of complex aminoguanidine-containing natural products

קבוצת guanidine הפונקציונלית, המוצגת ביותר בהבלטת ארגינין חומצת אמינו, אחת מאבני הבניין הבסיסיים של חיים, היא מרכיב מבני חשוב נמצא הרבה מוצרים ותרופות טבע מורכבים. בשל הגילוי המתמיד של מוצרים טבעיים guanidine המכיל חדשים ומולקולות קטנות נועדו, שיטות guanidinylation מהירות ויעילות הן עניין להוט כימאים אורגניים סינטטיים מרפאים. מכיוון nucleophilicity ו הבסיסי של guanidines יכולים להשפיע טרנספורמציות כימי עוקבות מסורתי, guanidinylation העקיף הוא נרדף בדרך כלל. שיטות עקיפות להעסיק צעדי הגנה מרובים נפוצות מעורבים מבשר אמין סמוי, כגון יזיד, phthalimide, או carbamate. תוך עקיפת שיטות עוקפות אלה והעסקת תגובה guanidinylation ישירה מוקדם ברצף סינתטי, ניתן היה לזייף את guanidine מסוף לינארי המכיל עמוד השדרה של clavatadine לממשסינתזה קצרה ויעילה של מעכב שיה גורם זה חזק. בפועל, hydrochloride guanidine מעובד באמצעות מערך הגנה שנבנה בקפידה כי הוא מותאם כדי לשרוד את השלבים הסינתטיים לבוא. בעריכת א clavatadine, guanidinylation הישירה של diamine הזמין מסחרי בוטלה שני צעדים מיותרים מן הסינתזה שלה. יחד עם המגוון הרחב של קבוצות הגנת guanidine הידוע, guanidinylation הישירה הצטיינה פרקטית תמציתית ויעילות הטמון לשיטות למצוא הביתה של ארגז כלי כימאי סינטטי.

Guanidinylation הישיר של α זמין מסחרי,-diamine ω, ואחריו תגובה עם triphosgene, ספק את isocyanate תגובתי 8 כמו החלק הליניארית של clavatadine (איור 1b). תשואות של רצף תגובת שני שלבים הם תמיד גבוהות, 95% או יותר. מגיב Guanidinylation 6 הוכן בדיוק כפי שתואר על ידי גודמ...

Watch this Scientific Journal Video about A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products at JoVE.com

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

ישיר, בשלבים מוקדמים Guanidinylation פרוטוקול לסינתזה של מוצרים טבעיים Aminoguanidine המכיל קומפלקס

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

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Universidad de Cartagena UDEC

Research

JoVE Journal

Chemistry

10.5K Views.  Central Washington University. Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol. 

Video: A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological processes. This subject embraces diverse scientific areas, spanning from physical, biological and bioorganic chemistry to biology and medicine, with applications to the amelioration of quality of life, health and aging. Multidisciplinary skills are required for the full investigation of the many facets of radical processes in the biological environment and chemical knowledge plays a crucial role in unveiling basic processes and mechanisms. We developed a chemical biology approach able to connect free radical chemical reactivity with biological processes, providing information on the mechanistic pathways and products. The core of this approach is the design of biomimetic models to study biomolecule behavior (lipids, nucleic acids and proteins) in aqueous systems, obtaining insights of the reaction pathways as well as building up molecular libraries of the free radical reaction products. This context can be successfully used for biomarker discovery and examples are provided with two classes of compounds: mono-trans isomers of cholesteryl esters, which are synthesized and used as references for detection in human plasma, and purine 5',8-cyclo-2'-deoxyribonucleosides, prepared and used as reference in the protocol for detection of such lesions in DNA samples, after ionizing radiations or obtained from different health conditions.

Radical-based biomimetic chemistry has been applied to building-up libraries necessary for biomarker development.

רדיקלים חופשיים בביולוגיה כימית: מהתנהגות כימית לפיתוח סמנים ביולוגיים

The involvement of free radicals in life sciences has constantly increased with time and has been connected to several physiological and pathological ...

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase

Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical probe that targets the enzyme&#39;s active sites. A reporter tag introduced into the probe allows for the detection of the labeled enzyme by in-gel fluorescence scanning, protein blot, fluorescence microscopy, or liquid chromatography-mass spectrometry. Here, we describe the preparation and use of the compound ARN14686, a click chemistry activity-based probe (CC-ABP) that selectively recognizes the enzyme N-acylethanolamine acid amidase (NAAA). NAAA is a cysteine hydrolase that promotes inflammation by deactivating endogenous peroxisome proliferator-activated receptor (PPAR)-alpha agonists such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). NAAA is synthesized as an inactive full-length proenzyme, which is activated by autoproteolysis in the acidic pH of the lysosome. Localization studies have shown that NAAA is predominantly expressed in macrophages and other monocyte-derived cells, as well as in B-lymphocytes. We provide examples of how ARN14686 can be used to detect and quantify active NAAA ex vivo in rodent tissues by protein blot and fluorescence microscopy.

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase

Here, we describe the preparation and use of an activity-based probe (ARN14686, undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl]carbamate) that allows for the detection and quantification of the active form of the proinflammatory enzyme N-acylethanolamine acid amidase (NAAA), both in vitro and ex vivo.

הכנה<em&gt; In vivo</em&gt; השתמש של Probe פעילות מבוססת עבור<em&gt; N</em&gt; -acylethanolamine חומצה Amidase

Activity-based protein profiling (ABPP) is a method for the identification of an enzyme of interest in a complex proteome through the use of a chemical ...

Biochemistry

An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this procedure amino functionalized 'lysine' and guanido functionalized 'arginine' peptoid monomers can be included within the same peptoid sequence. This procedure uses on-resin (N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) or Dde protection, orthogonal conditions to the Boc protection of lysine monomers. Subsequent deprotection allows an efficient on-resin guanidinylation reaction to form the arginine residues. The procedure is compatible with the commonly used submonomer method of peptoid synthesis, allowing simple peptoids to be made using common laboratory equipment and commercially available reagents. The representative synthesis, purification and characterization of two mixed peptoids is described. The evaluation of these compounds as potential anti-infectives in screening assays against Leishmania mexicana is also described. The protozoan parasite L. mexicana is a causative agent of cutaneous leishmaniasis, a neglected tropical disease that affects up to 12 million people worldwide.

A protocol to synthesize peptoids with mixed cationic functionality in the same sequence is presented (lysine- and arginine-type monomers). Subsequent testing of these compounds against Leishmania mexicana, the protozoan parasites that cause cutaneous leishmaniasis, is also described.

שיטה יעילה עבור הסינתזה של Peptoids עם מעורב ליזין מסוג / ארגינין-סוג מונומרים וערכה של אנטי-leishmanial פעילותם

This protocol describes the manual solid-phase synthesis of linear peptoids that contain two differently functionalized cationic monomers. In this ...

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

שינויו Functionalization של קבוצת guanidine ידי מבשרי תפורות

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

סינתזה מפוצלת וברכה ואפיון של הספרייה אמידה השלישון פפטיד

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide sequences. Synthesis of some unnatural amino acids often includes the use of a precursor consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains can be installed on an amino acid backbone found in this Schiff-base complex. The resulting unnatural amino acid can then be isolated from this complex using hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic solution. These highly acidic conditions may remove acid-labile side-chain protecting groups necessary for the unnatural amino acids to be used in microwave-assisted solid-phase peptide synthesis. In this work, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff base complex. Hydrolysis conditions presented in this work are suitable for retention of acid-labile side-chain protecting groups and may be adaptable to a variety of unnatural amino acid substrates.

Here, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff-base complex. Hydrolysis conditions presented here are suitable for use when retention of acid-labile side-chain protecting groups is required. This technique may be adaptable to a variety of unnatural amino acid substrates.

הידרוליזה של תנאי Ni-שיף-Base מורכבים באמצעות מתאים שמירת חומצה-רָפִיף קבוצות הגנה

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide ...

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

The synthesis of polyamine-based peptide amphiphiles (PPAs) is a significant challenge due to the presence of multiple amine nitrogens, which requires judicious use of protecting groups to mask these reactive functionalities. In this paper, we describe a facile method for the preparation of these new class of self-assembling molecules.

פרוטוקול נתיישב לסינתזה של הרכבה עצמית מבוסס פוליאמין פפטיד חומרים פעילי שטח (PPAs), Biomaterials קשורים

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). ...

The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and functionalize polymer chains with compounds that are able to improve biocompatibility, mechanical properties, or cell viability allows the design of novel materials to meet new challenges in the biomedical field. With the polymer functionalization strategies, click chemistry is a powerful tool to improve cell-compatibility and drug delivery properties of polymeric devices. Similarly, the fundamental need of biomedicine to use sterile tools to avoid potential adverse-side effects, such as toxicity or contamination of the biological environment, gives rise to increasing interest in the microwave-assisted strategy.
The combination of click chemistry and the microwave-assisted method is suitable to produce biocompatible hydrogels with desired functionalities and improved performances in biomedical applications. This work aims to synthesize RGD-functionalized hydrogels. RGD (arginylglycylaspartic acid) is a tripeptide that can mimic cell adhesion proteins and bind to cell-surface receptors, creating a hospitable microenvironment for cells within the 3D polymeric network of the hydrogels. RGD functionalization occurs through Huisgen 1,3-dipolar cycloaddition. Some PAA carboxyl groups are modified with an alkyne moiety, whereas RGD is functionalized with azido acid as the terminal residue of the peptide sequence. Finally, both products are used in a copper catalyzed click reaction to permanently link the peptide to PAA. This modified polymer is used with carbomer, agarose and polyethylene glycol (PEG) to synthesize a hydrogel matrix. The 3D structure is formed due to an esterification reaction involving carboxyl groups from PAA and carbomer and hydroxyl groups from agarose and PEG through microwave-assisted polycondensation. The efficiency of the gelation mechanism ensures a high degree of RGD functionalization. In addition, the procedure to load therapeutic compounds or biological tools within this functionalized network is very simple and reproducible.

We present a protocol for the synthesis of RGD-functionalized hydrogels as devices for cell and drug delivery. The procedure involves copper catalyzed alkyne-azide cycloaddition (CuAAC) between alkyne-modified polyacrylic acid (PAA) and a RGD-azide derivative. The hydrogels are formed using microwave-assisted polycondensation and their physicochemical properties are investigated.

הסינתזה של RGD פונקציונלית הידרוג ככלי יישומים טיפוליים

The use of polymers as biomaterials has provided significant advantages in therapeutic applications. In particular, the possibility to modify and ...

Bioengineering

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very difficult and laborious to make aziridines in optically pure forms on a large scale to apply asymmetric synthesis of aza compounds. Fortunately, we successfully achieved both enantiomers (2R)- and (2S)-aziridine-2-carboxylates with the electron-donating &#945;-methylbenzyl group at the ring nitrogen as non-activated aziridines. These starting aziridines have two distinct functional groups-highly reactive three-membered ring and versatile carboxylate. They are applicable in ring-opening or ring-transformation with aziridine and in functional group transformation to others from carboxylate. Both of these enantiomers were utilized in the preparation of biologically important amino acyclic and/or aza-heterocyclic compounds in an asymmetric manner. Specifically, this report describes the first expedient asymmetric synthesis of both enantiomers of 5, 6-dihydrouracil-type marine natural products biemamide B and D as potential TGF-&#946; inhibitors. This synthesis consisted of regio- and the stereoselective ring-opening reaction of aziridine-2-carboxylate and subsequent formation of 4-aminoteterahydropyrimidine-2,4-dione. One more example in this protocol dealt a highly stereoselective Mukaiyama reaction of aziridine-2-carboxylate and silyl enol ether, following intramolecular aziridine ring-opening to provide easy and facile access to (-)-epiallo-isomuscarine.

Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine

In this study, we prepare both enantiomers of aziridine-2-carboxylate, which are used in the asymmetric synthesis of alkaloids, including biemamide B and D, and (-)-epiallo-isomuscarine.

הכנת אזירידינים לא פעילים של אננטיופור וסינתזה של ביאמאמיד B, D ואפיאלו-איזומוסקרין

Nitrogen-containing heterocycle aziridines are synthetically very valuable for the preparation of azacyclic and acyclic molecules. However, it is very ...

Preparation of 1&deg; Amines: Azide Synthesis

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum hydride, or by catalytic hydrogenation to primary amines. The driving force for such reactions is the elimination of nitrogen gas.
Azide synthesis also works with other electrophiles like epoxides to produce amino alcohols through stereoselective ring-opening reactions. Alkyl azides have an explosive nature and must be carefully handled.

Preparation of 1&amp;deg; Amines: Azide Synthesis

הכנת 1° אמינים: סינתזת אזיד

Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide ...