کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10771116 | 1050838 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Protection against malaria induced by chirally modified Plasmodium falciparum's MSP-142 pseudopeptides
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The C-terminal portion of the Plasmodium falciparum blood stage MSP-1 antigen plays a key role in invasion of human erythrocytes. The MSP-11282-1301 non-polymorphic 1585 peptide, from the processed MSP-142 fragment, is poorly immunogenic and highly α-helical [Angew. Chem. Int. Ed. 40 (2001) 4654]. Assessing the α-carbon asymmetry and its implication in the host immune response is proposed in this work to overcome the 1585 peptide's immunological properties. Accordingly, the effect of incorporating single d-amino acids and Ï-[CH2-NH] isoster bonds into the 1585 peptide was examined both at the immunogenic and 3D-structure levels. Therefore, specific binding to RBCs is promoted by site-directed chiral modifications on the native peptide as well as by simultaneously combining specific d-substitutions with Ï-[CH2-NH] isoster bonds transforming this molecule into a high specific HLAβ1*1101 allele binder. d-analog pseudopeptide immunized animals induced antibodies selectively recognizing a recombinant as well as native MSP-142 and MSP-133 fragments. Protection and low parasitemia levels were induced in Aotus monkeys immunized with the EVLYL(dK)PLAGVYRSLKKQLE analog. Peptide α-carbon chiral transformation is therefore an important target for structural modulation and, consequently, represents a novel approach towards designing multi-component subunit-based malarial vaccines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 3, 15 April 2005, Pages 1053-1066
Journal: Biochemical and Biophysical Research Communications - Volume 329, Issue 3, 15 April 2005, Pages 1053-1066
نویسندگان
José Manuel Lozano, Fabiola Espejo, Ricardo Vera, Luis Eduardo Vargas, Jaiver Rosas, Liliana Lesmes, Elizabeth Torres, Jimena Cortés, Yolanda Silva, Manuel Elkin Patarroyo,