模拟胞壁酰肽的十五肽的鉴定。

Identification of pentadecapeptide mimicking muramyl peptide.

作者信息

Laman Alexander Georgievich, Shepelyakovskaya Anna Olegovna, Berezin Igor Anatolevich, Boziev Khanafi Magometovich, Rodionov Igor Leonidovich, Chulina Irina Alexandrovna, Malakhova Galina Vladimirovna, Brovko Fedor Alexandrovich, Murashev Arkadi Nikolaevich, Korpela Timo Kalevi, Nesmeyanov Vladimir Andreevich

机构信息

Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki 6, Puschino, Moscow Region 142290, Russia.

出版信息

Vaccine. 2007 Apr 12;25(15):2900-6. doi: 10.1016/j.vaccine.2006.08.030. Epub 2006 Sep 1.

DOI:10.1016/j.vaccine.2006.08.030

PMID:17005302

Abstract

We used monoclonal antibody, generated against N-acetylglucosaminyl-beta1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP), and phage display libraries of random peptides to select for oligopeptides, that mimic GMDP in their biological activity. Selected phage clones displayed a peptide RVPPRYHAKISPMVN (called RN-peptide) on their surface. This peptide was synthesized. RN-peptide was shown to augment the antibody response to ovalbumin in mice while the peptide was non-immunogenic and non-pyrogenic. We also characterized adjuvant activity of 14-, 10- and 7-mer analogs of RN-peptide truncated at the C-terminus and found them to be active. Because both carbohydrate and peptide fragments are critical for the biological activity of muramyl peptides, the results indicate that RN-peptide mimicks the spatial structure of intact GMDP.

摘要

我们使用针对N-乙酰葡糖胺-β1-4-N-乙酰胞壁酰-丙氨酰-D-异谷氨酰胺（GMDP）产生的单克隆抗体，以及随机肽的噬菌体展示文库来筛选在生物活性上模拟GMDP的寡肽。筛选出的噬菌体克隆在其表面展示了一种肽RVPPRYHAKISPMVN（称为RN肽）。合成了这种肽。结果表明，RN肽可增强小鼠对卵清蛋白的抗体反应，同时该肽无免疫原性和致热原性。我们还对在C端截短的RN肽的14肽、10肽和7肽类似物的佐剂活性进行了表征，发现它们具有活性。由于碳水化合物和肽片段对胞壁酰肽的生物活性都至关重要，因此结果表明RN肽模拟了完整GMDP的空间结构。