Identification of pentadecapeptide mimicking muramyl peptide.
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.
Laman
Alexander Georgievich
AG
Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki 6, Puschino, Moscow Region 142290, Russia.
Shepelyakovskaya
Anna Olegovna
AO
Berezin
Igor Anatolevich
IA
Boziev
Khanafi Magometovich
KM
Rodionov
Igor Leonidovich
IL
Chulina
Irina Alexandrovna
IA
Malakhova
Galina Vladimirovna
GV
Brovko
Fedor Alexandrovich
FA
Murashev
Arkadi Nikolaevich
AN
Korpela
Timo Kalevi
TK
Nesmeyanov
Vladimir Andreevich
VA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D011749:Pyrogens / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D019151:Peptide Library; D011749:Pyrogens; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C023868:N-acetyl-beta-glucosaminyl-N-acetylmuramyl-alanylisoglutamine