The physiological anti-hypertensive peptide catestatin and its common human variant Gly364Ser: differential cardiovascular effects in a rat model of hypertension.

Catestatin (CST), a 21-amino acids physiological peptide, has emerged as a key modulator of cardiovascular functions due to its anti-hypertensive and cardioprotective properties. However, the ramifications of the most common human variant of CST (viz., Gly364Ser) on cardiovascular pathophysiology remain partially understood.

AITF (4-acetamidophenyl triflimide) mediated synthesis of amides, peptides and esters.

A simple, broadly applicable protocol for amidation and esterification reactions is described. Thereby, 4-acetamidophenyl triflimide (AITF), a crystalline stable reagent, is employed for the activation of carboxylic acids. The use of AITF as a coupling agent is demonstrated in the synthesis of peptides, amides and esters under mild conditions in good to excellent yields.

Synthesis of N-Protected Amino Sulfenyl Methyl Formamides and Sulfonyl Methyl Formamides: A Simple Protocol.

Chiral amino acid-derived formamides represent one of the most versatile components in multicomponent reactions. Herein, we describe a facile synthesis of N-protected amino sulfenyl methyl formamides and sulfonyl methyl formamides the Mannich reaction of N-protected amino alkyl thiols followed by oxidation using 3-chloroperbenzoic acid (-CPBA). This protocol is applicable to a wide range of Fmoc- and Cbz-protected amino acids.

Thioacids - synthons for amide bond formation and ligation reactions: assembly of peptides and peptidomimetics.

The synthesis of α-amino thioacids and peptide thioacids and their applications in chemoselective amide bond formation, ligation of peptides/proteins/glycopeptides and synthesis of peptidomimetics are reviewed. A variety of successful methods including both C-terminal and N-terminal activations for the coupling of α-amino thioacids and peptide thioacids have ascertained the thioacid-based protocol as a benign alternative to some of the traditional methods of amide/peptide bond formation which employs carboxyl activation. In addition to the couplings involving unprotected peptide fragments and solid phase synthesis, their use in the synthesis of different classes of peptidomimetics such as thioxopeptides, imide conjugates and acylsulfonamide-peptide conjugates only illustrates the versatility of this functionality in generating diverse classes of molecules, some of which are relevant to drug discovery and chemical biology.

Computational studies on ground and excited state charge transfer properties of peptidomimetics.

Chemical modifications at various peptide positions result in peptidomimetics with unique physical and chemical properties that can be used for a range of applications. Among many peptidomimetics, ureidopeptides are interesting due to their ability to act as donor-bridge-acceptor systems through which charge transfer occurs in one direction and can be triggered by an electrochemical pulse without perturbing the nuclear position. In this regard, some UP mimetics with different chromophoric units are studied in this work to understand their role using DFT based methods.

N-Chlorosuccinimide-Mediated Oxidative Chlorination of Thiols to Nα -Protected Amino Alkyl Sulfonyl Azides and Their Utility in the Synthesis of Sulfonyl Triazole Acids.

An efficient oxidative chlorination of thiols to Nα-protected amino alkyl sulfonyl azides is delineated. The reaction involves in situ generation of sulfonyl chloride employing Nchlorosuccinimide and tetrabutylammonium chloride-water in acetonitrile, followed by the reaction with sodium azide. The protocol is simple, straight forward, mild and high yielding.

Computational Studies on Structural, Excitation, and Charge-Transfer Properties of Ureidopeptidomimetics.

Peptides with ureido group enclosing backbones are considered peptidomimetics and are known for their higher stabilities, biocompatibilities, antibiotic, inhibitor, and charge-transduction activities. These peptidomimetics have some unique applications, which are quite different from those of natural peptides. Hence, it is imperative to appreciate their properties at a microscopic level.

A facile one pot route for the synthesis of imide tethered peptidomimetics.

A simple and efficient method for the synthesis of N,N'-orthogonally protected imide tethered peptidomimetics is presented. The imide peptidomimetics were synthesized by coupling the in situ generated selenocarboxylate of N(α)-protected amino acids with N(α)-protected amino acid azides in good yields. The protocol was also successfully applied for the synthesis of hybrid tripeptidomimetics bearing both amide and imide functionalities.

Observation of a reversible isomorphous phase transition and an interplay of "σ-holes" and "π-holes" in Fmoc-Leu-ψ[CH2-NCS].

Fmoc-Leu-ψ[CH2NCS] undergoes a reversible isomorphous phase transition upon cooling. The crystal structure at 100 K displays a short N=C=S···N=C=S intermolecular interaction, which has been characterized based on experimental charge density analysis, as a stabilizing interaction with both σ-holes and π-holes acting cooperatively.

Synthesis and stereochemistry-activity relationship of chiral thiourea derivatives as potential anticancer agents.

Synthesis of new chiral thiourea derivatives (27 examples) as anticancer agents has been described. Three compound 7d (NSC code 761448/1), 7e1 (NSC code 767161/1), and 7e3 (NSC code 767160/1) were found to exhibit higher anticancer activity than 5-fluorouracil against Colon cancer, Melanoma, Ovarian cancer, and Breast cancer subpanels. The effect of stereochemistry of amino acid residues on the tumor growth inhibitory activity has also been studied.

Epimerization free synthesis of O-acyl isodipeptides employing COMU.

O-Acyl isodipeptides are prepared by coupling Boc-Ser/Thr-OBzl with Fmoc-Xaa-OH employing COMU, well known third generation peptide coupling agent. The reaction proceeds with high yield and the chemical homogeneity of the synthesized molecules were established via chiral HPLC analyses. The O-acyl isodipeptide units play crucial role in the success of ' click peptide' protocol employed for assembling ' difficult sequence' peptides.

Synthesis of selenoxo peptides and oligoselenoxo peptides employing LiAlHSeH.

Synthesis of selenoxo peptides by the treatment of N(α)-protected peptide esters with a combination of PCl(5) and LiAlHSeH is delineated. The method is simple, high-yielding, and free from racemization. Thus obtained selenoxo peptides are used as units for N-terminal chain extension through N(α)-deprotection/coupling to yield peptide-selenoxo peptide hybrids.

Iron(III) catalysed synthesis of unsymmetrical di and trisubstituted ureas--a variation of classical Ritter reaction.

An application of the classical Ritter reaction for the synthesis of unsymmetrical di and trisubstituted ureas catalyzed by FeCl(3) is described. The protocol is of significant interest in view of the easy availability of precursors, mild reaction conditions employed and interestingly its applicability for the alkylation of alcohols capable of forming stable carbocationic intermediates even to the sterically hindered moieties.

CuI-promoted one-pot synthesis of N-Boc protected β-ketotriazole amino acids: application in the synthesis of new class of dipeptidomimetics.

One-pot click chemistry of N(α)-Boc-bromomethylketones, NaN3 and propiolic acid affords N-Boc protected 1,4-disubstituted 1,2,3-β-ketotriazole acids in good to excellent yield. The use of CuI as catalyst and DMSO as solvent leads the click reaction to efficient, practical and column-free preparation of the title compounds. The utility of the resulting unnatural amino acids as building blocks to prepare triazole possessing peptidomimetics is also delineated.

Characterization of Nα-Fmoc-protected dipeptide isomers by electrospray ionization tandem mass spectrometry (ESI-MS(n)): effect of protecting group on fragmentation of dipeptides.

A series of positional isomeric pairs of Fmoc-protected dipeptides, Fmoc-Gly-Xxx-OY/Fmoc-Xxx-Gly-OY (Xxx=Ala, Val, Leu, Phe) and Fmoc-Ala-Xxx-OY/Fmoc-Xxx-Ala-OY (Xxx=Leu, Phe) (Fmoc=[(9-fluorenylmethyl)oxy]carbonyl) and Y=CH(3)/H), have been characterized and differentiated by both positive and negative ion electrospray ionization ion-trap tandem mass spectrometry (ESI-IT-MS(n)). In contrast to the behavior of reported unprotected dipeptide isomers which mainly produce y(1)(+) and/or a(1)(+) ions, the protonated Fmoc-Xxx-Gly-OY, Fmoc-Ala-Xxx-OY and Fmoc-Xxx-Ala-OY yield significant b(1)(+) ions. These ions are formed, presumably with stable protonated aziridinone structures.

Carbonyldiimidazole (CDI) mediated synthesis of Nα-protected amino acid azides: application to the one-pot preparation of ureidopeptides.

Synthesis of Nα-protected amino acyl azides starting from corresponding acids via the carbonyldiimidazole (CDI) activation is described. The protocol is extended for a one-pot preparation of ureido peptides that circumvents the isolation of acyl azide and isocyanate intermediates. The reaction was accomplished without using any additives and base.

Synthesis of oligopeptides through O-acyl isopeptide method.

The O-acyl isopeptide method has recently gained attention as an efficient protocol for the synthesis of 'difficult sequence' peptides. Herein, synthesis of three oligopeptides of different length, a pentapeptide Gly-Leu-Leu-Ser-Val, a heptapeptide fragment 285-291 of transmembrane (M7-24-T40) Ala-Val-Leu-Ser-Leu-Pro-Leu and a decapeptide, Gly-Leu-Leu-Ser-Val-Leu-Gly-Ser-Val-Ala were demonstrated in solution phase by employing O-acyl isopeptide method. The peptides were established through an efficient pH triggered intramolecular O→N acyl migration under physiological conditions.

Poly(vinyl)chloride supported palladium nanoparticles: catalyst for rapid hydrogenation reactions.

Palladium nanoparticles supported over poly(vinyl)chloride matrix (PVC-Pd(0)) are prepared through an efficient and inexpensive protocol. The catalyst has been characterized by XRD, SEM and TEM and its utility for the reduction of a range of functional groups as well as for the removal of some common protecting groups employed in peptide chemistry is demonstrated.

Characterization of Nα-Fmoc-protected ureidopeptides by electrospray ionization tandem mass spectrometry (ESI-MS/MS): differentiation of positional isomers.

Four pairs of positional isomers of ureidopeptides, FmocNH-CH(R(1))-ϕ(NH-CO-NH)-CH(R(2))-OY and FmocNH-CH(R(2))-ϕ(NH-CO-NH)-CH(R(1))-OY (Fmoc = [(9-fluorenyl methyl)oxy]carbonyl; R(1) = H, alkyl; R(2) = alkyl, H and Y = CH(3)/H), have been characterized and differentiated by both positive and negative ion electrospray ionization (ESI) ion-trap tandem mass spectrometry (MS/MS). The major fragmentation noticed in MS/MS of all these compounds is due to --N--CH(R)--N--bond cleavage to form the characteristic N- and C-terminus fragment ions. The protonated ureidopeptide acids derived from glycine at the N-terminus form protonated (9H-fluoren-9-yl)methyl carbamate ion at m/z 240 which is absent for the corresponding esters.

Isoselenocyanates derived from amino acid esters: an expedient synthesis and application to the assembly of selenoureidopeptidomimetics, unsymmetrical selenoureas and selenohydantoins.

An important class of organoselenium compounds-α-isoselenocyanato esters 4 has been prepared by a reaction of α-isocyano esters with elemental selenium powder. The reaction issimple, rapid and all the isoselenocyanates have been isolated as stable ones after chromatographic purification. These hitherto unreported classes of molecules would be useful building blocks for the preparation of variety of selenium containing peptidomimetics.

New and simple synthesis of acid azides, ureas and carbamates from carboxylic acids: application of peptide coupling agents EDC and HBTU.

Conversion of carboxylic acids into acid azides using peptide coupling agents, EDC and HBTU is described. The procedure is efficient, practical and applicable to a diverse range of carboxylic acids including N-protected amino acids. Using the same reagents, one-pot synthesis of ureas, dipeptidyl urea esters and carbamates from acids has also been achieved.

Click chemistry aided synthesis of 1,4-substituted 1,2,3-triazole based N-Fmoc protected epsilon-amino acids: isolation, characterization and synthesis of novel triazole based unnatural amino acids.

A new class of 1,4-substituted 1,2,3-triazole-based unnatural amino acids is demonstrated by employing click reaction between N-Fmoc amino alkyl azides and propiolic acid. The resulting unnatural amino acids were isolated and then subjected to Fmoc deprotection to isolate 1,2,3-triazole based amino acids as stable solids. These new class of molecules were also used for chain extension from both N- and C-terminals to synthesize dipeptidomimetics bearing 1,2,3-triazole moiety in the backbone.

Application of carbodiimide mediated Lossen rearrangement for the synthesis of alpha-ureidopeptides and peptidyl ureas employing N-urethane alpha-amino/peptidyl hydroxamic acids.

Application of the Lossen rearrangement to the synthesis of N-urethane protected alpha-peptidyl ureas and ureidopeptides is reported. The carbodiimide mediated rearrangement of N-Boc/Z/Fmoc protected alpha-amino/peptide hydroxamic acids into isocyanates and coupling of the latter with the amino acid esters/peptide esters have been accomplished in a single-pot to obtain good yields of urea products. Synthesis of the ureidoalanine derivatives via the hydroxamate derivatives of N-protected aspartic acid has also been carried out using the same procedure.