title: Understanding the Boron-Nitrogen Interaction and Its Possible Implications in Drug Design.
abstract: 2-Aminoethoxydiphenylborate (2-APB) is a broad-spectrum modulator of various membrane proteins. Specifically, it exhibits concentration dependent modulation of calcium signaling through store-operated calcium (SOC) channels: low micromolar concentration of 2-APB stimulates SOC entry while a higher concentration induces complete inhibition. Ab initio quantum chemical calculations show that the relative stability of the two major isomers of 2-APB (cyclic and extended) is about 8 kcal/mol. The dual functionality of 2-APB for SOC channels is thus likely associated with its ability to switch among isomeric forms, suited to different binding sites in the SOC channels with distinct binding affinities. Importantly, the moderate relative stability of different isomers results from a delicate balance between the intramolecular boron-nitrogen coordinate bond with strength about -45 kcal/mol and ring strain engendered by cyclic oligomerization. The synergistic effect of these two factors likely makes 2-APB an ideal dual effect drug.
authors.affiliation: Kuang Yaming Honors School, Nanjing University , Nanjing, P.R. China.|Institute for Computational Molecular Science, Temple University , 1900 North 12th Street, Philadelphia, Pennsylvania 19122-6078, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Dong
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Physics, Temple University , 1900 North 12th Street, Philadelphia, Pennsylvania 19122-6078, United States.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute for Computational Molecular Science, Temple University , 1900 North 12th Street, Philadelphia, Pennsylvania 19122-6078, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein