Engineering of a synthetic receptor to alter peptide binding selectivity.

Engineering of a synthetic receptor to alter peptide binding selectivity.
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改造合成受体以改变肽结合选择性。

DOI:
10.1016/1074-5521(95)90270-8
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发表时间:
1995
影响因子:
--
通讯作者:
Still,WC
Still,WC
中科院分区:
生物1区
文献类型:
--
作者:
Carrasco,MR;Still,WC

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BackgroundMolecular recognition processes ae ubquitous in nature: substrate binding by enzymes, antigen recognition by antibodies. and hormone activation of receptors provide three clmic examples. To better understand these large systems it is valuable to study Mueller. dell defined host molecules. I’revioucly Eve found sequence-selective peptide binding\vith J cl, lss of C, symmetric synthetic receptors. In this work Eve rCitionally altered that host structure in order to product CI corresponding change in binding selectivity.ResultsA novel C, symmetric receptor\L’JF designed md synthesized such that. unlike previous host mole-cules, it contained hydrogen-bond accepting functionality within the binding cavity. Screening of thic host against a combinatorial tripeptide library revealed m csquisite selectrvlty for cequences with I)-Pro-I>-Asn carboxyl termini.(: omputer simulations and NMK studies indicntc that hydrogen bonding of the~)-A\rl side-chain. lmide to the xnine functionJity Lvithin the avity is responsible for this selectivity.ConclusionsComputer-aided design dud combimtoridI library- screening methods combine to provide. I powerful, ipproach to induce md evaluate the results of rational changes in the moleculx- recognition properties of molecules. Using this approach,\ve modified the binding properties of a cln5s of molecules to select For hydrogeli-bonding residues Instead of hydrophobic residues and conconlitmtly increased the overall sequence selectivity. Structural studies indicate that these changes indeed result from the type of binding mode proposed JS pa-t of the initial design. Thi5 approxh cnn increase our understanding of molecular recognition processes, and thould alloy the rational design of larger, more selective systems.
DOI: 10.1021/ja00080a044
发表时间: 1994
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发表时间: 1995
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影响因子: --
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