Short-chain peptides are transported across membranes through promiscuous proton-dependent oligopeptide transporters (POTs)--a subfamily of the major facilitator superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the absorption of various drugs in the gut as well as transport to target cells. Here, we present a structure of an oligomeric POT transporter from Shewanella one...

In this paper, a [2.2.1] bicyclic core is applied as a peptidomimetic scaffold capable of reproducing the structural relationship between the critical residues of the Tat protein, in an effort to create small molecules capable of binding to TAR RNA and inhibiting the Tat/TAR interaction. A systematic twenty-member panel mimicking an Arginine-Aspartic acid (R-D) moiety was synthesized and the ab...

Cyclic peptidomimetic compounds have been investigated utilizing ab initio Hartree Fock molecular orbital calculations. Prospective use of these ionophores as curative drugs for Alzheimer's disease has been investigated by considering their metal toxicity removal efficiency. A (2,4,2,4) system that is, ((gly-et)-(ala-gly-gly-et))2 with CH2NH backbone is predicted to undergo low conformational r...

Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline)-DKP (diketopiperazine)-based peptidomimetic scaffold capable of arranging in an unusual α-turn conformation. The synthesis is based on a diastereoselective Pictet-Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complet...

The insect kinins are potent diuretic peptides that preferentially form a cis-Pro, type VI beta-turn. An insect kinin analog containing (2S,4S)-4-aminopyroglutamate, a novel cis-peptide bond, type VI beta-turn motif, demonstrates significant activity in the physiological range in a cricket diuretic assay. This is the first instance of a 4-aminopyroglutamate analog of a peptide with a preference...

The discovery of numerous endogenous neuropeptides that participate in the formation, transmission, modulation, and perception of pain signals offers numerous strategies for the development of new analgesics. Nevertheless, the same research has not yet replaced opioids as the gold standard of pain treatment. Therefore, one possible avenue of drug development may shift interest from searching fo...

Boceprevir (SCH 503034; SCH-503034) is a peptidomimetic NS3/4A serine protease inhibitor, representing a new class of hepatitis C virus (HCV) inhibitors. It is being developed by Merck & Co. as part of a combination therapy regimen for the treatment of HCV infections. In two phase III trials, the HCV RESPOND-2 and HCV SPRINT-2 trials, the primary endpoints were met. Phase III development contin...

Introduction RGD peptidomimetics conjugated to Inand Y-DOTA complexes, and to Gd-DTPA complex, have been recently developed to target the αvβ3 receptor. In this work, we describe the grafting of a new RGD peptidomimetic on ultrasmall particles of iron oxide (USPIO) coated with 3,3’-bis(phosphonate)propionic acid in the context of magnetic resonance molecular imaging.The grafting rates have been...

Herein we describe the synthesis and HIV-1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV-1 wild-type and multimutated ANAM-11 proteases obtained to date for this class of molecules (∼40 nM for wild-t...