Cyclic RGD-containing peptides: in silico exploration against BCL-X(L)

Abstract

Сyclic peptides attract attention for possible applications in cancer treatment. We examined the abili­ty of six cyclic RGD-containing peptides-based compounds to inhibit B-cell lymphoma-extra-large (Bcl-XL) (PDB ID: 3zk6) using the in silico method. We observed that the addition of electron withdrawing group (–Cl) to cyclic RGD-containing peptides-based compound induced a radical improvement in the hydrogen bond strength with Arg139 in Bcl-XL. Compound F with -9.2 kcal/mol was observed to be positioned at the best-docked site in the binding pocket of Bcl-XL and therefore suggested to have greater potential anticancer abili­ty than other studied compounds as well as the referenced compound (Doxorubicin). The ADMET properties of compound F and Doxorubicin were investigated and reported. Our findings may open door for the design and development of library of efficient cyclic RGD-containing peptides-based drug-like compounds as potential anti- cancer agents. Keywords: Bcl-X(L), carcinogesis, cyclic RGD peptides, in silico study, modeling­, peptide-protein interaction