Ca-mediated thiolysis of peptide–resin linkage as an option for preparing protected peptide thioesters

A mild new procedure for preparing protected peptide thioesters, based on Ca²⁺-assisted thiolysis of peptide–Kaiser oxime resin (KOR) linkage, is described. Ac-Ile-Ser(Bzl)-Asp(OcHx)-SR (Ac: acetyl; Bzl: benzyl; cHx: cyclohexyl), model peptide, was readily released from the resin by incubating the peptide–KOR at 60 °C in mixtures of DMF with n-butanethiol [R = (CH₂)₃CH₃] or ethyl 3-mercaptopropionate [R = (CH₂)₂COOCH₂CH₃] containing Ca(CH₃COO)₂. After serine and aspartic acid side-chain deprotection under acid conditions, Ac-Ile-Ser-Asp-S(CH₂)₂COOCH₂CH₃ was successfully obtained with good quality and high yield. This type of C-terminal modified peptide may act as an excellent acyl donor in peptide segment condensation by the thioester method, native chemical ligation and enzymatic methods.     

A facile strategy to prevent trifluoroacetylation of N-terminal proline peptides

Unwanted trifluoroacetylation occurred at the N-terminus of prolinyl peptides during detachment from the solid phase. This was observed when the N-α-Fmoc protecting group had been removed prior to the final TFA treatment. Subtly changing the SPPS protocol and incorporating Boc- in place of the Fmoc-protected proline as the N-terminal building block efficiently suppressed this side reaction.     

Intermolecular Communication on a Liposomal Membrane: Enzymatic Amplification of a Photonic Signal with a Gemini Peptide Lipid as a Membrane‐Bound Artificial Receptor

A supramolecular system that can activate an enzyme through photo‐isomerization was constructed by using a liposomal membrane scaffold. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, which provided a scaffold for the system, was prepared by self‐assembly of a photoresponsive receptor and a cationic synthetic lipid. NADH‐dependent L ‐lactate dehydrogenase, the signal amplifier, was immobilized on the liposomal surface by electrostatic interactions. Recognition of photonic signals by the membrane‐bound receptor induced photo‐isomerization, which significantly altered the receptor’s metal‐binding affinity. The response to the photonic signal was transmitted to the enzyme by Cu²⁺ ions. The enzyme amplified the chemical information through a catalytic reaction to generate the intended output signal.     

An expedient synthesis of peptidyl N-alkylamides by "HOPE" strategy

We have developed an expedient approach,"HOPE"(hybrid orthogonal protocol with ease) strategy for the synthesis of peptidyl N-alkylamides.This new strategy was characterized by following points:incorporating Boc and Fmoc protocols together on Merrifield resin,removal of SPG(side-chain protecting groups) without the damage of linker structure on the resin,and the ammonolysis of linker as the last step could achieve the introducing N-alkylamide structure into C-terminal and releasing product from resin-support simultaneously.In present work,eight peptidylamides with different alkylsubstitution at C-terminal were conveniently synthesized by HOPE strategy.     

Synthesis and characterization of a novel imidazole cyclic trimer

A novel cyclic trimer of imidazole 1, in which imidazole rings are connected by amide bonds, has been synthesized with the help of LiCl as a template for the cyclization. The absorption spectra of 1 indicate the extension of conjugation between imidazole rings and amide bonds. The addition of 3 M equiv of MgCl₂ solubilizes 1 in polar organic solvent, suggesting the chelating ability of 1 to Mg cation.     

Colorimetric Sensing by Using Allosteric‐DNAzyme‐Coupled Rolling Circle Amplification and a Peptide Nucleic Acid–Organic Dye Probe

Target detection by the naked eye : The action of an RNA‐cleaving allosteric DNAzyme in response to ligand binding was coupled to a rolling circle amplification process to generate long single‐stranded DNA molecules for colorimetric sensing (see scheme). Upon hybridization of the resulting DNA with a complementary PNA sequence in the presence of a duplex‐binding dye, the color of the dye changed from blue to purple.

     

Dissociation mechanisms and implication for the presence of multiple conformations for peptide ions with arginine at the C‐terminus: time‐resolved photodissociation study

Time‐resolved photodissociation (PD) patterns of singly protonated peptides with arginine at the C‐terminus (C‐arg peptide ions) have been used to classify the dissociation channels into two categories, i.e. high‐energy channels generating v, w and x and low‐energy ones generating b, y and z. x + 1 formed by C_α? CO cleavage seems to be the intermediate ion in high‐energy channels just as a + 1 is for N‐arg peptide ions. Difference in time‐resolved pattern indicates that the two sets of channels, high‐ and low‐energy ones, are not in direct competition. Noncompetitive dissociation is also indicated by the observation of anomalous effect of matrix used in matrix‐assisted laser desorption ionization, a cooler matrix generating more high‐energy product ions both in spontaneous dissociation and in PD. Results from detailed investigation suggest that the two sets of channels start from two (or more) different conformations. Copyright © 2010 John Wiley & Sons, Ltd.     

Hemostatic Efficacy of Biological Self‐Assembling Peptide Nanofibers in a Rat Kidney Model

We evaluated the hemostatic efficacy of a biological self‐assembling peptide RADA16‐I in a rat kidney injury model. Adult male rats were randomized into five groups: sham operation (no renal excision), no hemostatic agent (control), commercially available gelatin sponge (Gelfoam), 1% RADA16‐I, and 2% RADA16‐I. After left partial nephrectomy, the anesthetized animal was anticoagulated using 300 IU · kg^?1 heparin, and the topical hemostatic agent was applied to the injury. Blood loss and mean arterial pressure (MAP) were recorded. As was the case for Gelfoam, 2% RADA16‐I produced marked hemostasis versus controls (p < 0.01). Blood loss with 1% and 2% RADA16‐I was significantly less than controls. The decline in MAP during surgery was less with 2% versus 1% RADA16‐I. RADA16‐I also resulted in less histological tissue responses than Gelfoam. These data suggest that RADA16‐I can stop hemorrhage, with only minimal tissue responses, in experimental renal injury.

     

Synthesis and Characterization of Enzymatically Degradable PEG‐Based Peptide‐Containing Hydrogels

Biodegradable hydrogels were synthesized by the click reaction of 4‐arm azido‐terminated PEG differing in molecular weight (2 100 and 8 800) and two alkyne‐terminated peptides: [alkyne]‐GFLGK‐[alkyne] and ([alkyne]‐GFLG)₂K. The physical properties of in situ formed hydrogels were examined. The hydrogels were highly elastic as determined by rheological and microrheological studies. Swelling degree and enzymatic degradation by papain were dependent on the molecular weight of the PEG, but not the peptide. For PEG8800‐based hydrogels, time‐course analysis of degradation showed that the molecular weight of the soluble fraction quickly reached the PEG precursor value. These findings may guide future design of hydrogels with controllable mechanical properties and enzymatic degradability.