Inhibition of Alzheimer's amyloid-ß peptide aggregation and its disruption by a conformationally restricted α/ß hybrid peptide.

Insertion of an anthranilic acid in an amyloidogenic peptide sequence generates a novel conformationally restricted α/ß-hybrid peptide that inhibits amyloid formation of Aß(1-40) and disrupts preformed fibrillar aggregates in vitro. Such ß-sheet breaker hybrid peptides (BSBHps) may be useful for designing novel physiologically important compounds relevant to diverse amyloidoses and for studying the process of aggregation.

Reversal of aggregation using ß-breaker dipeptide containing peptides: Application to Aß(1-40) self-assembly and its inhibition.

Reversion of protein or peptide aggregation is a formidable task, important in various domains of research at the interface of chemistry, medicine, and nanoscience. A novel class of dipeptides, termed as ß-breaker dipeptides (BBDPs), is identified, which can be incorporated into the self-recognizing sequences to generate a novel class of conformational switch which forms ß-sheet at an initial stage and then converts in a controlled manner to random coil at specific conditions. Incorporation of BBDPs in a well designed amyloidogenic peptides generates a special class of ß-sheet breaker peptides those undergo a chemical change at physiological condition generating a breaker element in situ. These ß-breaker peptides are shown to first incorporate into the amyloid and then disrupt it. Such conformational switches may be used to study agrregation/disaggregation process and may find many biomedical applications relevant to aggregation related disorders. Such strategy for reversion of peptide aggregation using chemical tricks may find application in material chemistry as well.

Phenolic ester mediated oligopeptide synthesis promoted by HOBt.

Although substituted phenolic ester mediated peptide synthesis is an efficient and well established method, the same via totally unsubstituted phenyl ester is not preferred due to the extremely slow rate of aminolysis. We have investigated the scope of the unsubstituted phenyl ester as an intermediate in peptide bond formation and found that it may be useful for the design of chemoselective peptide ligation when HOBt is used as an acyl transfer catalyst. The scope of HOBt catalyzed, oxo ester mediated ligation is explored for the synthesis of oligopeptides containing a cysteine, serine and threonine at the N-terminus of the ligating peptide.