当前位置：
X-MOL 学术
›
J. Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Tuning the Biological Activity of RGD Peptides with Halotryptophans†
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-12-24 , DOI: 10.1021/acs.jmedchem.0c01536 Isabell Kemker 1 , David C. Schröder 1 , Rebecca C. Feiner 2 , Kristian M. Müller 2 , Antoine Marion 3 , Norbert Sewald 1, 3
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-12-24 , DOI: 10.1021/acs.jmedchem.0c01536 Isabell Kemker 1 , David C. Schröder 1 , Rebecca C. Feiner 2 , Kristian M. Müller 2 , Antoine Marion 3 , Norbert Sewald 1, 3
Affiliation
|
An array of l- and d-halotryptophans with different substituents at the indole moiety was synthesized employing either enzymatic halogenation by halogenases or incorporation of haloindoles using tryptophan synthase. Introduction of these Trp derivatives into RGD peptides as a benchmark system was performed to investigate their influence on bioactivity. Halotryptophan-containing RGD peptides display increased affinity toward integrin αvβ3 and enhanced selectivity over integrin α5β1. In addition, bromotryptophan was exploited as a platform for late-stage diversification by Suzuki–Miyaura cross-coupling (SMC), resulting in new-to-nature biaryl motifs. These peptides show enhanced affinity toward αvβ3, good affinity to αvβ8, and remarkable selectivity over α5β1 and αIIbβ3 while featuring fluorogenic properties. Their feasibility as a probe was demonstrated in vitro. Extensive molecular dynamics simulations were undertaken to elucidate NMR and high-performance liquid chromatography (HPLC) data for these late-stage diversified cyclic RGD peptides and to further characterize their conformational preferences.
中文翻译：
用卤代色氨酸调节RGD肽的生物活性†
使用通过卤化酶的酶促卤化或使用色氨酸合酶掺入卤代吲哚来合成在吲哚部分具有不同取代基的1-和d-卤代色氨酸的阵列。将这些Trp衍生物引入RGD肽作为基准系统以研究其对生物活性的影响。含Halotryptophan-RGD肽显示增加的亲和力朝向整合素α v β 3和增强的过整合素α选择性5 β 1。另外，铃木色氨酸被铃木-宫浦交叉耦合（SMC）开发为后期多样化的平台，从而产生了新的自然的联芳基序。这些肽显示出增强的朝向α亲和力v β 3，良好的亲和力，以α v β 8，和显着的选择性超过α 5 β 1和α IIB β 3，同时具有荧光性质。在体外证明了其作为探针的可行性。进行了广泛的分子动力学模拟，以阐明这些后期多样化的环状RGD肽的NMR和高效液相色谱（HPLC）数据，并进一步表征其构象偏好。
更新日期：2021-01-14
中文翻译：
用卤代色氨酸调节RGD肽的生物活性†
使用通过卤化酶的酶促卤化或使用色氨酸合酶掺入卤代吲哚来合成在吲哚部分具有不同取代基的1-和d-卤代色氨酸的阵列。将这些Trp衍生物引入RGD肽作为基准系统以研究其对生物活性的影响。含Halotryptophan-RGD肽显示增加的亲和力朝向整合素α v β 3和增强的过整合素α选择性5 β 1。另外，铃木色氨酸被铃木-宫浦交叉耦合（SMC）开发为后期多样化的平台，从而产生了新的自然的联芳基序。这些肽显示出增强的朝向α亲和力v β 3，良好的亲和力，以α v β 8，和显着的选择性超过α 5 β 1和α IIB β 3，同时具有荧光性质。在体外证明了其作为探针的可行性。进行了广泛的分子动力学模拟，以阐明这些后期多样化的环状RGD肽的NMR和高效液相色谱（HPLC）数据，并进一步表征其构象偏好。
京公网安备 11010802027423号