Oldenburg K R, Loganathan D, Goldstein I J, Schultz P G, Gallop M A
Department of Bioorganic Chemistry, Affymax Research Institute, Palo Alto, CA 94304.
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5393-7. doi: 10.1073/pnas.89.12.5393.
Peptide ligands for the carbohydrate-binding protein concanavalin A (Con A) have been identified by screening a large, diverse peptide library expressed on the surface of filamentous phage. A dodecapeptide containing the consensus sequence Tyr-Pro-Tyr was found to bind Con A with an affinity (dissociation constant, Kd) of 46 microM, comparable to that of a known carbohydrate ligand, methyl alpha-D-mannopyranoside (Kd of 89 microM). In addition the peptide inhibited precipitation of the alpha-glucan dextran 1355 by Con A. Given the complexity of oligosaccharide synthesis, the prospect of finding peptides that competitively inhibit carbohydrate-specific receptors may simplify the development of new therapeutic agents.
通过筛选在丝状噬菌体表面表达的大型多样肽库，已鉴定出用于碳水化合物结合蛋白伴刀豆球蛋白A（Con A）的肽配体。发现一个含有共有序列Tyr-Pro-Tyr的十二肽以46微摩尔的亲和力（解离常数，Kd）结合Con A，与已知碳水化合物配体α-D-甘露吡喃糖苷甲基酯（Kd为89微摩尔）相当。此外，该肽抑制Con A对α-葡聚糖右旋糖酐1355的沉淀作用。鉴于寡糖合成的复杂性，寻找竞争性抑制碳水化合物特异性受体的肽的前景可能会简化新型治疗剂的开发。
