Selection and characterization of a peptide-based complement modulator targeting C1 of the innate immune system.

ABSTRACT: The human complement pathway plays a pivotal role in immune defence, homeostasis, and autoimmunity regulation, and complement-based therapeutics have emerged as promising interventions, with both antagonistic and agonistic approaches being explored. The classical pathway of complement is initiated when the C1 complex binds to hexameric antibody platforms. Recent structural data revealed that C1 binds to small, homogeneous interfaces at the periphery of the antibody platforms. Here, we have developed a novel strategy for complement activation using macrocyclic peptides designed to mimic the interface between antibodies and the C1 complex. In vitro selection utilizing the RaPID system identified a cyclic peptide (cL3) that binds to the C1 complex via the globular head domains o

SUBMITTER: Hamers SMWR 

PROVIDER: S-EPMC11289891 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature