Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

被引:11
作者
Curtidor, Hernando [1 ,2 ]
Reyes, Cesar [1 ]
Bermudez, Adriana [1 ,2 ]
Vanegas, Magnolia [1 ,2 ]
Varela, Yahson [1 ,3 ]
Patarroyo, Manuel E. [1 ,4 ]
机构
[1] Colombian Inst Immunol Fdn FIDIC Nonprofit Making, Bogota 111321, Colombia
[2] Univ Rosario, Sch Med & Hlth Sci, Bogota 111321, Colombia
[3] Appl & Environm Sci Univ UDCA, Fac Hlth Sci, Bogota 111321, Colombia
[4] Univ Nacl Colombia, Fac Med, Bogota 111321, Colombia
关键词
synthetic peptides; therapeutics; immunogenicity; malaria vaccine; structure; PLASMODIUM-FALCIPARUM MALARIA; MEROZOITE SURFACE PROTEIN-1; CLASS-II MOLECULES; MHC CLASS-I; T-CELL-RECEPTOR; RED-BLOOD-CELLS; SYNTHESIZED ANTIMALARIAL VACCINE; CHAIN CONFORMATIONAL ENTROPY; LINKED-IMMUNOSORBENT-ASSAY; MONKEY AOTUS-NANCYMAAE;
D O I
10.3390/molecules22122199
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions' immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparumconserved regions binding to host cells. Conserved high activity binding peptides' (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo-electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or -interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.
引用
收藏
页数:31
相关论文
共 269 条
[1]   Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania [J].
Acosta, CJ ;
Galindo, CM ;
Schellenberg, D ;
Aponte, JJ ;
Kahigwa, E ;
Urassa, H ;
Schellenberg, JRMA ;
Masanja, H ;
Hayes, R ;
Kitua, AY ;
Lwilla, F ;
Mshinda, H ;
Menendez, C ;
Tanner, M ;
Alonso, PL .
TROPICAL MEDICINE & INTERNATIONAL HEALTH, 1999, 4 (05) :368-376
[2]   LEFT-HANDED POLYPROLINE-II HELICES COMMONLY OCCUR IN GLOBULAR-PROTEINS [J].
ADZHUBEI, AA ;
STERNBERG, MJE .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 229 (02) :472-493
[3]   Polyproline-II Helix in Proteins: Structure and Function [J].
Adzhubei, Alexei A. ;
Sternberg, Michael J. E. ;
Makarov, Alexander A. .
JOURNAL OF MOLECULAR BIOLOGY, 2013, 425 (12) :2100-2132
[4]   Electrostatic potential as a tool to understand interactions between malaria vaccine candidate peptides and MHC II molecules [J].
Agudelo, William A. ;
Galindo, Johan F. ;
Patarroyo, Manuel E. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 410 (03) :410-415
[5]   Population genetic analysis of large sequence polymorphisms in Plasmodium falciparum blood-stage antigens [J].
Ahouidi, Ambroise D. ;
Bei, Amy K. ;
Neafsey, Daniel E. ;
Sarr, Ousmane ;
Volkman, Sarah ;
Milner, Dan ;
Cox-Singh, Janet ;
Ferreira, Marcelo U. ;
Ndir, Omar ;
Premji, Zul ;
Mboup, Souleymane ;
Duraisingh, Manoj T. .
INFECTION GENETICS AND EVOLUTION, 2010, 10 (02) :200-206
[6]   Modifying RESA protein peptide 6671 to fit into HLA-DRβ1 pockets induces protection against malaria [J].
Alba, MP ;
Salazar, LM ;
Vargas, LE ;
Trujillo, M ;
Lopez, Y ;
Patarroyo, ME .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 315 (04) :1154-1164
[7]   6746 SERA peptide analogues immunogenicity and protective efficacy against malaria is associated with short α helix formation:: Malaria protection associated with peptides a helix shortening [J].
Alba, MP ;
Salazar, LM ;
Puentes, A ;
Pinto, M ;
Torres, E ;
Patarroyo, ME .
PEPTIDES, 2003, 24 (07) :999-1006
[8]   Retrotranslocation of MHC class I heavy chain from the endoplasmic reticulum to the cytosol is dependent on ATP supply to the ER lumen [J].
Albring, J ;
Koopmann, JO ;
Hämmerling, GJ ;
Momburg, F .
MOLECULAR IMMUNOLOGY, 2004, 40 (10) :733-741
[9]   Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses [J].
Alexander, J ;
del Guercio, MF ;
Maewal, A ;
Qiao, L ;
Fikes, J ;
Chesnut, RW ;
Paulson, J ;
Bundle, DR ;
DeFrees, S ;
Sette, A .
JOURNAL OF IMMUNOLOGY, 2000, 164 (03) :1625-1633
[10]  
Allen P M, 1989, Int Immunol, V1, P141, DOI 10.1093/intimm/1.2.141