Texas A & M University, Chemistry Department, P.O. Box 30012, College Station, Texas 77842, USA.
Chem Soc Rev. 2011 Aug;40(8):4411-21. doi: 10.1039/c0cs00218f. Epub 2011 Apr 11.
Many "new generation" peptidomimetics are designed to present amino acid side chains only; they do not have structural features that resemble peptide main chains. These types of molecules have frequently been presented in the literature as mimics of specific secondary structures. However, many "side-chain only" peptidomimetics do not rest in single conformational states, but exist in a limited number of freely interconverting forms. These different conformations may resemble different secondary structures, so referring to them as, for instance, turn- or helical-mimics understates the ways they could adapt to various binding situations. Sets of scaffolds that can be used to mimic aspects of nearly every secondary structure, i.e. universal peptidomimetics, can be constructed. These may assume a privileged place in library design, particularly in high throughput screening for pharmacological probes for which binding conformations, or even the target itself, is unknown at the time the library is designed (critical review, 101 references).
许多“新一代”肽类似物仅设计用于呈现氨基酸侧链；它们没有类似于肽主链的结构特征。这些类型的分子在文献中经常被呈现为特定二级结构的模拟物。然而，许多“仅侧链”肽类似物并不处于单一构象状态，而是存在于数量有限的自由互变形式中。这些不同的构象可能类似于不同的二级结构，因此将它们称为例如，转折或螺旋模拟物并不能充分说明它们适应各种结合情况的方式。可以构建可以用于模拟几乎所有二级结构的方面的一组支架，即通用肽类似物。在文库设计中，它们可能占据一个特殊的位置，特别是在高通量筛选中，对于药理探针，在设计文库时，结合构象甚至是目标本身都是未知的（综述，101 篇参考文献）。
