Synthesis of the ‘southern’ tripeptide of Cyclomarins A and C having novel anti-tuberculocidal mode of action

The synthesis of the ‘southern’ tripeptide of Cyclomarins A and C has been described which includes two unusual amino acids. The unusual amino acids have been synthesized and coupled with l-alanine to obtain the tripeptide.     

Synthesis of guanidinium-derived receptor libraries and screening for selective peptide receptors in water

A library of "tweezer" receptors, incorporating a guanidinium "head group" and two peptide derived side arms has been prepared on the solid-phase using an orthogonally protected guanidinium scaffold 12. The library was screened with various tripeptide derivatives in an aqueous solvent system. A tweezer receptor 25 for the side chain protected tripeptide 19 was identified from the screening experiments. Receptor 25 was resynthesised and solution binding studies were carried out, which revealed that 25 binds to tripeptide 19 with K(a)=8.2 x 10(4) +/- 2.5 x 10(4) (15 % DMSO/H(2)O, pH 8.75) and with appreciable selectivity over the tripeptide enantiomer 22 and the side chain deprotected tripeptide 20.     

Pyrrolidinone-modified di- and tripeptides: highly diastereoselective preparation and investigation of their stability

Pyrrolidine-2,4-diones have been identified as a novel starting point for the synthesis of peptide analogues. This paper describes a method for the efficient and diastereoselective incorporation of this moiety into peptide chains to furnish di- and tripeptide analogs. The stability of these pyrrolidinone modified di- and tripeptides was found to be markedly improved when compared to that of a natural peptide. In addition, solid phase peptide synthesis employing a pyrrolidinone containing tripeptide is demonstrated.     

Synthesis of L-α-aminoadipyl-L-serinyl-D-valine,a naturally occuring tripeptide from the fermentation of Penicillium chrysogenum

A new tripeptide, L -α-aminoadipyl-L -seryl-D-valine has been synthesized by coupling the protected L-seryl-D -valine dipeptide with an appropriately protected L -α-aminoadipic acid ester. The free tripeptide was obtained after treatment with liquid HF and purification by HPLC.     

Polyisocyanides derived from tripeptides of alanine

Helical polymers of isocyanotripeptides derived from alanine have been synthesized and their architectures studied in detail. The helical conformation of the polyisocyanotripeptides is stabilized by internal hydrogen-bonding arrays between the tripeptide side chains. The possibility of extending the well-defined hydrogen-bonded array, from dipeptide to tripeptide side chains, depends strongly on the stereochemistry of the constituent alanine amino acids, as has been shown by circular dichroism and IR studies. In polymers containing a weaker hydrogen-bonding array adjacent to the polymer backbone, due to steric interactions between the alanine methyl groups, a stronger second hydrogen-bonding array was present between the peptide bonds furthest away from the main chain, which is probably a result of stretching/compression of the helical-polymer conformation.     

A synthetic tripeptide as a novel organo-gelator: a structural investigation

A self-associating synthetic tripeptide [Boc-Ala(1)-Aib(2)-β-Ala(3)-OMe (Aib: α-amino-isobutyric acid, β-Ala: β-alanine)] forms thermoreversible transparent gels in various organic solvents and this offers the first example of a peptide gelator whose molecular self-assembly afforded for gelation has been characterised by single-crystal X-ray diffraction and FT-IR and NMR spectroscopic studies. The crystal structure of an analogous synthetic non-gelator tripeptide [Boc-Ala(1)-Gly(2)-β-Ala(3)-OMe] is also discussed in light of the self-assembly of the gelator tripeptide.     

Assembly of a trifunctional artificial peptide into an anti-parallel duplex with three Cu(II) cross-links

Analogous to self-assembly in natural DNA or proteins, we describe the synthesis of a heterofunctional artificial tripeptide that self-assembles into an antiparallel duplex by coordination of three Cu(II) ions. The tripeptide contains three pendant ligands, pyridine (py), methyl bipyridine (bpy), and terpyridine (tpy), in series on an aminoethylglycine (aeg) backbone. These ligands chelate three Cu(II) ions, forming two [Cu(tpy)(py)](2+) and one [Cu(bpy)(2)](2+) complexes, that cross-link two tripeptide strands to give a trimetallic supramolecular structure. The tripeptide and metal-linked tripeptide duplex are characterized with NMR spectroscopy, mass spectrometry, and analytical high performance liquid chromatography (HPLC). Spectrophotometric titrations are used to quantitatively examine the stoichiometry of binding. Together with electron paramagnetic resonance (EPR) spectroscopy, the identities of the Cu(II) complexes and their environments are examined. The EPR spectrum reveals a significant amount of coupling between metal centers compared to a dimetallic dipeptide analogue. EPR and UV-vis absorbance spectroscopy, together with molecular modeling, provide evidence that the tripeptide acts as a scaffold to hold the metal centers in close proximity.     

Synthesis of Macrocyclic Ttipeptidopyridine Schiff Base Candidates

Russian Journal of General Chemistry - In the current study, a series of macrocyclic tripeptide Schiff bases 2–6 were synthesized by using macrocyclic tripeptide hydrazide 1 as starting...     

Analysis of delta-L-alpha-aminoadipyl-L-cysteinyl-D-valine by ion chromatography and pulsed amperometric detection

A novel high-performance liquid chromatography (HPLC) method is presented for the detection and trace level determination of the tripeptide delta-L-alpha-aminoadipyl-L-cysteinyl-D-valine (ACV). The tripeptide, an intermediate in penicillin production, is derived from fungal fermentation. The technique relies on ion-exchange separation of the tripeptide on an anion-exchange column followed by detection by reduction on a gold electrode using pulsed amperometry. The sensitivity of direct determination of ACV is increased by employing pulsed amperometric detection (PAD) over direct ultraviolet detection. Choice of the working electrode and optimisation of electrode potentials was based on cyclic voltammograms recorded for the tripeptide in the mobile phase. A linear regression equation was obtained over the range 0-100 micrograms ml-1. The detection limit in fermentation broths was found to be 0.1 micrograms ml-1 whereas in buffer the detection limit was found to be 10 ng ml-1. A good correlation coefficient was observed when ACV concentrations determined by ion chromatography-PAD were compared with measurements obtained by pre-column derivatisation with fluoromethylorthochloroformate followed by HPLC separation on a reversed-phase C18 silica column with UV detection. The procedure has been applied to the measurement of natural levels of ACV in fermentation broths of selected strains of Aspergillus nidulans and Penicillin chrysogenum.     

Structural analysis of the tripeptide glycyle-methionyl-glycine (H-Gly-Met-Gly-OH) and its hydrochloride

As part of an investigation on the coordination ability of peptides, structural analyses of the solid tripeptide glycyl-methionyl-glycine (H-Gly-Met-Gly-OH) and its hydrochloride have been carried out. The quantum chemical calculations (B3LYP/6-31+G(d) and UHF/6-31G^**) and linear-dichroic infrared (IR-LD) spectroscopy predict a near to linear structure of the pure ligand, but the experimental IR-LD data are in accordance with a cross-linked disposition of both amide fragments in the protonated form. This result is confirmed by an X-ray diffraction study of latter compound. The presented work also demonstrates the possibilities of IR-LD spectral analysis for the structural characterization of an amorphous system such as the investigated tripeptide.     

An investigation of contributions to carbon-13 spin-lattice relaxtion in amino acids and peptide hormones

Carbon-13 spin-lattice relaxation times have been measured in glycine and the tripeptide pro-leu-gly-NH₂. These times are compared with those measured in the same compounds where the glycine α-carbon has been deuterated. In this manner evidence is obtained which indicates that mechanisms other than dipolar interactions with covalently bonded protons may contribute to carbon-13 spin-lattice relaxation. The effect of these additional mechanisms is found to be non-negligible for the carbonyl carbon of glycine and the glycine α-carbon of the tripeptide. The implication of these findings for deducing motional information from carbon-13 relaxation measurements is briefly discussed.     

A Dithienylethene‐Based Rewritable Hydrogelator

Dithienylethene photochromic switching units have been incorporated into a hydrogelating system based on a tripeptide motif. The resulting hybrid system provided both a photochromic response and the ability to gelate water under acidic and neutral conditions. Fluorescence spectroscopy shows that the dithienylethene units are in sufficient proximity to each other to stack in gel fibers, with the tripeptide unit determining solubility. TEM measurements provided insight into the microscopic structure of the fibers formed.     

A differential array of metalated synthetic receptors for the analysis of tripeptide mixtures

A novel library of resin-bound receptors within a cross-reactive differential array for the identification and discrimination of tripeptides and tripeptide mixtures is reported. Pattern recognition using principal component analysis showed complete discrimination of four similar tripeptides and three tripeptide mixtures. The library is comprised of a Cu(II)-centered core with two proximally appended tripeptide arms emanating outward. One tripeptide arm was prepared using combinatorial chemistry to generate the differential nature of the library. Thirty resin-bound receptors were randomly selected from the library and placed within a silicon microchip array that included integrated microfluidics elements, and an indicator-uptake assay was used for colorimetric signaling. The indicator Orange G yielded an accurate measure of the degree of association between receptors and analytes as determined by kinetic analysis of the indicator-uptake assays. Within this paper we detail the method used for differential sensing using a novel receptor library. This work further demonstrates the power and utility of a differential array of synthetic receptors for identification and discrimination of complex bioanalytes.     

A new and general method for the synthesis of tripeptide aldehydes based on the multi-component Ugi reaction

Tripeptide aldehydes, such as Z-Leu-Leu-Leu-H (MG-132), are an important class of compounds due to their biological activity. A new, general method for the synthesis of tripeptide aldehydes based on the multi-component Ugi reaction was developed. A careful choice of isocyanides makes it possible to obtain tripeptide precursors whose functionalization led to target structures. This method can be used for the preparation of tripeptide aldehydes with non-natural amino acid side chains.     

Comparison of amino acid sequence analysis by electron ionization and negative-ion chemical ionization mass spectrometry

The positive electron ionization and negative chemical ionization mass spectra of 15 different derivatives of the tripeptide Phe-Ala-Leu have been compared. Total ion currents and ion currents of sequence-characterizing ions have been measured and compared. The negative-ion spectra, using 10% carbon dioxide in argon as moderator gas, proved to be simpler and contained more abundant sequence ions than the positive electron ionization spectra.     

Sub-ppt detection limits for copper ions with Gly-Gly-His modified electrodes

An electrochemical metal ion sensor has been developed with a detection limit of less than 0.2 ppt by the covalent attachment of the tripeptide Gly-Gly-His as a recognition element to a 3-mercaptopropionic acid modified gold electrode.     

Production, analysis, and application of spatially resolved shells in solid-phase polymer spheres

Two-photon fluorescence microscopy has been used to interrogate the interior functionality of polymer resin beads. By employing this technique, the spatial distribution of the initial functionality contained within the polymer matrix has been determined. Spatially resolved, concentric shells were then produced synthetically in these polymer spheres via a series of protection/deprotection reactions in which two-photon fluorescence microscopy was employed to monitor each successive step. To demonstrate the potential utility of these techniques in combinatorial screening, a set of beads was prepared containing a unique tripeptide sequence in each of the three concentric shells within each individual bead. The set was then screened for the binding affinity of each tripeptide toward a fluorescent ligand.     

Intramolecular ditryptophan crosslinks enforce two types of antiparallel beta structures.

BACKGROUND: Two types of biaryl crosslinks can be formed with natural protein sidechains: ditryptophan and dityrosine. Biaryl crosslinks have the same topology as disulfide crosslinks, yet little is known about their effect on local peptide structure. RESULTS: Three ditryptophan-linked peptide dimers based on the sequence Ac-Leu-Trp-Ala-COX were prepared. The tripeptide dimer with -CONH(2) termini was too insoluble to study, but the tripeptide dimer with -COOMe termini crystallized from methanol/chloroform as an antiparallel beta-sheet. The tripeptide dimer with a -CONMe(2) termini adopted a slipped antiparallel beta structure in methanol/chloroform. CONCLUSIONS: These results suggest that intermolecular ditryptophan crosslinks that join the middle of peptide chains can confer a preference for antiparallel beta-sheet structure. The effect is most dramatic when both the inside and outside edges of the dimer can form hydrogen bonds as in the crystal structure of dimer 3b.     

Synthesis of Anisolylated Aspartyl and Glutamyl Tripeptides

A process has been developed for transforming the beta-carboxyl of aspartate and the gamma-carboxyl of glutamate into anisolyl ketones. These ketones are occasional byproducts in peptide synthesis, resulting from deprotection or resin-removal processes in the presence of anisole as a scavenger. The ketone amino acids have been incorporated in a tripeptide by coupling with CBMIT. During peptide bond formation the keto group of the glutamyl residue required protection, which was provided as the ethylene dithioketal.     

Self-assembled fluorescent tripeptide nanoparticles for bioimaging and drug delivery applications

Peptide self-assembled nanomaterials have attracted more and more attention due to their wide applications such as drug delivery, cell imaging, and real-time drug monitoring. However, the application of the peptide is still limited by its inherent optical properties. Here we proposed and prepared a series of fluorescent tripeptide nanoparticles (TPNPs) through π-π stacking and zinc coordination. The experimental results show that the nanoparticles (TPNPs1) formed by the self-assembly of the tripeptide tryptophan-tryptophan-tryptophan have the highest fluorescence intensity, uniform and appropriate size, and low cytotoxicity. Furthermore, there was fluorescence resonance between TPNPs1 and doxorubicin, which has been successfully applied for real-time cell imaging and drug release monitoring.