期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 133, 期 42, 页码 17087-17092出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja207825y
关键词
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资金
- National Science Foundation [CHE-0748483]
- Welch Foundation [W-1640]
- Henry Dreyfus Teacher-Scholar Awards Program
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0748483] Funding Source: National Science Foundation
This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-amino-methyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20-30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (K-d) value of 0.95 nM in neutral phosphate buffer. Structure-activity studies revealed that three functional groups work in a positively cooperative manner to achieve this extraordinary stability (1) the N-terminal ammonium group, (2) the side chain ammonium group, and (3) the peptide backbone. Addition of the aminomethyl group to Phe substantially improved the selectivity for peptide versus amino acid and for an N-terminal vs nonterminal position. Importantly, Q7 binds to N-terminal AMPhe several orders of magnitude more tightly than any of the canonical amino acid residues. The high affinity, single-site selectivity, and small modification in this system make it attractive for the development of minimal affinity tags.
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