BPC-157 and Novel Hybrid Analogs CIARA-1, CIARA-2 Competitively Inhibit Acetylcholinesterase

Inhibiting Acetylcholinesterase (AChE) is a cornerstone therapeutic strategy for managing neurodegenerative disorders like Alzheimer's disease (AD), where cholinergic dysfunction is prominent. Current treatments often have side effects or limited efficacy, highlighting the need for novel compounds. BPC-157, a gastric pentadecapeptide with known pleiotropic effects, presents a unique scaffold. This study explored BPC-157 and its rationally designed hybrid analogs as potential AChE inhibitors to address this therapeutic gap.

Researchers investigated the AChE inhibitory potential of BPC-157 and two novel hybrid analogs, CIARA-1 and CIARA-2, in vitro. The hybrid peptides were designed to enhance interactions with the enzyme's active and peripheral binding sites by combining a BPC-157 fragment with an arginine-containing C-terminal sequence. Enzyme kinetics were assessed using a modified Ellman assay, and inhibition parameters were determined via Lineweaver-Burk analysis to characterize the inhibition mechanism and potency.