T1 - Efficient parallel synthesis of macrocyclic peptidomimetics

Synthesis of peptidomimetics, δ- And ε-lactam …
Photo provided by Flickr

Modular synthesis of cyclic peptidomimetics inspired …

2. Peptidomimetic development - With the information obtained from the peptide optimization, Mimotopes will explore a number of modifications, including bioisosteres, modified terminal endings, and amino acid modifications to increase the stability, bioavailability and pharmacokinetics of the leading compound(s). This process also includes the use of cyclic peptides, an approach which has been successful in the development of drugs which are now on market. Mimotopes has developed proprietary technology for the efficient synthesis of collections of C-N cyclic peptides, ideal for this phase of the project.

T1 - Design, synthesis and biological evaluation of glutathione peptidomimetics as components of anti-Parkinson prodrugs
Photo provided by Flickr

Synthesis of peptides and peptidomimetics (eBook, …

The Smith Group focuses on three principal research areas: (A) development of innovative synthetic methods having wide application; (B) demonstration of the utility of these synthetic tactics for the rapid construction of architecturally complex natural and unnatural products having significant bio-regulatory properties, and (C) novel bioorganic/medicinal chemistry programs, including non-peptide peptidomimetics (i.e., early examples of foldemers) in collaboration with the late Professor Ralph Hirschmann, programs relating to neurodegenerate diseases including Alzhemer’s and tauopathologies, in collaboration with Professors Virginia Lee and John Trojanowski (University of Pennsylvania School of Medicine), studies to inhibit HIV cellular entry (an NIH funded Program Project, involving colleagues at Harvard, Columbia, Bryn Mawr, Drexel, and Johns Hopkins), and projects on peptide/protein folding with Professor Robin Hochstrasser (Penn Chemistry). In each of the collaborative programs, Smith and his students exploit the power of “state-of-the-art” organic synthesis to provide solutions to biomedical programs of importance for the improvement of human health.

The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart.
Photo provided by Flickr

N2 - A new method for solid phase parallel synthesis of chemically and conformationally diverse macrocyclic peptidomimetics is reported. A key feature of the method is access to broad chemical and conformational diversity. Synthesis and mechanistic studies on the macrocyclization step are reported.

T1 - The synthesis of 'tyrosyl' peptidomimetics by acid-catalyzed N(1)-C(4) ring opening of 4-(4′-hydroxyphenyl)-azetidine-2-ones
Photo provided by Flickr

Efficient parallel synthesis of macrocyclic peptidomimetics

N2 - γ-Lactam peptidomimetic 2 of Pro-Leu-Gly-NH2 (PLG) was substituted at the 3-position with isobutyl, butyl, and benzyl moieties to give the PLG peptidomimetics 3-5, respectively. These compounds were synthesized to test the hypothesis that attaching a hydrophobic moiety to the lactam ring to mimic the isobutyl side chain of the leucyl residue of PLG would increase the dopamine receptor modulating activity of such peptidomimetics. These peptidomimetics were tested for their ability to enhance the binding of [3H]-N-propylnorapomorphine to dopamine receptors isolated from bovine striatal membranes. The rank order of effectiveness of the 3-substituent was benzyl > n-butyl > isobutyl > H.

Design, synthesis and evaluation of peptidomimetics …

Various techniques for generation of peptide and peptidomimetic libraries are summarized in this article. Multipin, tea bag, and split- couple-mix techniques represent the major methods used to make peptides and peptidomimetics libraries. The synthesis of these libraries were made in either discrete or mixture format. Peptides and peptidomimetics combinatorial libraries were screened to discover leads against a variety of targets. These targets, including bacteria, fungus, virus, receptors, and enzymes were used in the screening of the libraries. Discovered leads can be further optimized by combinatorial approaches.

Synthesis of Novel Amino Acids and Peptidomimetics …

A new construct for imitating a natural peptide ligand using a modified retro-inverso sequence is described. It is demonstrated through the synthesis of a peptidomimetic derived from the endogenous sequence of leucine enkephalin. The product was active at 400 nM and selective for μ-opioid receptors.

and synthesis of peptidomimetics, ..

Macrocyclic peptidomimetics are largely underrepresented in current small-molecule screening collections owing primarily to synthetic intractability; thus novel molecules based around these structures represent targets of significant interest, both from a biological and a synthetic perspective.