Báo cáo khoa học: Alternative binding proteins: Biological activity and therapeutic potential of cystine-knot miniproteins Harald Kolmar

Alternative Binding Proteins: Biological Activity and Therapeutic Potential of Cystine-Knot Miniproteins

Author: Harald Kolmar

Affiliation: Clemens-Schöpf-Institut für Biochemie und Organische Chemie, Technische Universität Darmstadt, Germany

Field: Biochemistry and Organic Chemistry

Abstract: This review explores cystine-knot miniproteins, a diverse family of small proteins characterized by a stable structural scaffold stabilized by three intramolecular disulfide bonds. These miniproteins exhibit a wide range of therapeutically useful biological activities and hold significant promise as scaffolds for developing novel therapeutics due to their intrinsic chemical and proteolytic stability. The review highlights successful engineering efforts in creating miniproteins with novel activities through functional loop grafting and directed evolution. Their small size facilitates both recombinant and chemical synthesis, enabling optimization of biological activity, specificity, and bioavailability via site-specific modifications, introduction of non-natural amino acids, or chemical conjugation. The structural features, natural biological activities, and potential for oral application of these miniproteins are discussed, alongside strategies for introducing novel bioactivities through protein engineering.

Keywords: conotoxin, cyclotide, cystine-knot, knottin, microprotein, miniprotein, squash inhibitor