biostudies-literatureDing LNational Natural Science Foundation of Chinathe Natural Science Foundation of Hubei Province23https://www.ebi.ac.uk/biostudies/studies/S-EPMC11769409biostudies-literatureUnknown17(1)Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy. The anticoagulation assay showed that the four P2' single-point mutants still had apparent inhibitory anticoagulation activity that selectively inhibited the human intrinsic coagulation pathway and had no influence on the extrinsic coagulation pathway or common coagulation pathway, wToxinsImprovement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.PMC1176940981973321 and 822044072021CFB130Chen ZLin YSun FZhai ZLuo HZhu WLuo XQin TYe XDing LShuang ZQin CfalseImprovement in XIa Selectivity of Snake Venom Peptide Analogue BF9-N17K Using P2' Amino Acid Replacements.Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy. The anticoagulation assay showed that the four P2' single-point mutants still had apparent inhibitory anticoagulation activity that selectively inhibited the human intrinsic coagulation pathway and had no influence on the extrinsic coagulation pathway or common coagulation pathway, w2025-01-01T00:00:00Z2025 Jan2025-04-05T09:33:26.418Z2025-04-05T09:33:26.418ZS-EPMC117694093985297610.3390/toxins17010023