Microarrays of tagged combinatorial triazine libraries in the discovery of small-molecule ligands of human IgG.
A novel and highly diverse tagged triazine library incorporating a triethylene glycol-based linker was synthesized using an orthogonal combinatorial approach on the solid phase and covalently immobilized on a glass substrate as a small molecule microarray (SMM). The SMM was screened with a fluorophore-conjugated human IgG, and 4 novel binders from a library of 2688 compounds were identified from the fully spatially addressable array without the need for compound decoding. Using surface plasmon resonance (SPR) analysis, binding seen on the array was confirmed, and a binding constant as low as Kd = 2.02 x10(-6) M was measured.
Uttamchandani
Mahesh
M
Department of Biological Sciences and Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore.
Walsh
Daniel P
DP
Khersonsky
Sonya M
SM
Huang
Xuan
X
Yao
Shao Q
SQ
Chang
Young-Tae
YT
D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D040081:Protein Array Analysis / Q000379:methods*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis*
D007074:Immunoglobulin G; D008024:Ligands; D014227:Triazines