Synthesis of - and ,-Heterocycle-Dipeptide Conjugates for Supramolecular Hydrogel Formation.

Small peptides with aromatic nuclei at the -terminus have been shown to form bioactive, biocompatible, and biodegradable supramolecular peptide hydrogels. Novel heterocycle-dipeptide conjugates with potential biological activity or application as drug carriers were synthesized by using (benzo[]thiophene) and ,(thieno [2,3-]pyridine and thieno[2,3-]quinoline) heterocycles as -protective groups for dipeptides l-Phe-l-Phe and l-Phe-l-Leu. The synthesis involved coupling heterocyclic carboxylic acids with trifluoroacetate salts of ethyl l-phenylalanyl-l-phenylalaninate and ethyl l-phenylalanyl- l-leucinate using HBTU and EtN, producing the corresponding six -heterocycle-dipeptide ester conjugates, which were then hydrolyzed to the carboxylic acids.

New Supramolecular Hydrogels Based on Diastereomeric Dehydrotripeptide Mixtures for Potential Drug Delivery Applications.

Self-assembly of peptide building blocks offers unique opportunities for bottom-up preparation of exquisite nanostructures, nanoarchitectures, and nanostructured bulk materials, namely hydrogels. In this work we describe the synthesis, characterization, gelation, and rheological properties of new dehydrotripeptides, Cbz--Lys(Cbz)-,-Asp-∆Phe-OH and (2-Naph)--Lys(2-Naph)-,-Asp-∆Phe-OH, containing a -terminal lysine residue --capped with carboxybenzyl (Cbz) and 2-Naphthylacetyl (2-Naph) aromatic moieties, an aspartic acid residue (Asp), and a -terminal dehydrophenylalanine (∆Phe) residue. The dehydrotripeptides were obtained as diastereomeric mixtures (,, and ,,Z), presumably via aspartimide chemistry.

Peptide-Based Supramolecular Hydrogels as Drug Delivery Agents: Recent Advances.

Supramolecular peptide hydrogels have many important applications in biomedicine, including drug delivery applications for the sustained release of therapeutic molecules. Targeted and selective drug administration is often preferential to systemic drug delivery, as it can allow reduced doses and can avoid the toxicity and side-effects caused by off-target binding. New discoveries are continually being reported in this rapidly developing field.

An injectable, naproxen-conjugated, supramolecular hydrogel with ultra-low critical gelation concentration-prepared from a known folate receptor ligand.

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels-self-assembled networks of fibrils able to trap water molecules. Typically, these hydrogelators can form stiff gels at concentrations of 0.1 to 1.