Multivalent recognition of peptides by modular self-assembled receptors.
Developing nontraditional approaches to the synthesis and characterization of multivalent compounds is critical to our efforts to study and interface with biological systems and to build new noncovalent materials. This paper demonstrates a biomimetic approach to the construction of discrete, modular, multivalent receptors via molecular self-assembly in aqueous solution. Scaffolds presenting 1-3 viologen groups recruit a respective 1-3 copies of the synthetic host, cucurbit[8]uril, in a noncooperative manner and with a consistent equilibrium association constant (K(a)) value of 2 x 10(6) M(-1) per binding site. The assembled mono-, di-, and trivalent receptors bind to their cognate target peptides containing 1-3 Trp residues with K(a) values in the range 1.7 x 10(4)-4.7 x 10(6) M(-1) and in predetermined mono- or multivalent binding modes with 31-280-fold enhancements in affinity and additive enthalpies due to multivalency. The extent of valency was determined directly by measuring the visible charge-transfer absorptivity due to the viologen-indole pair. The predictable behavior of this system and its ease of synthesis and analysis make it well suited to serve as a model for multivalent binding and for the multivalent recognition of peptides by design.
Reczek
Joseph J
JJ
Department of Chemistry, Trinity University, San Antonio, Texas 78212, USA.
Kennedy
Aimee A
AA
Halbert
Brian T
BT
Urbach
Adam R
AR
D001665:Binding Sites; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D018000:Receptors, Peptide / Q000737:chemistry*; D014755:Viologens / Q000737:chemistry*; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
D001952:Bridged-Ring Compounds; D007093:Imidazoles; D010455:Peptides; D018000:Receptors, Peptide; D014755:Viologens; C507198:cucurbit(8)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils