Mapping the anatomy of a Plasmodium falciparum MSP-1 epitope using pseudopeptide-induced mono- and polyclonal antibodies and CD and NMR conformation analysis

Lozano, José Manuel; Espejo, Fabiola; Ocampo, Marisol; Salazar, Luz Mary; Tovar, Diana; Barrera, Nubia; Guzmán, Fanny; Patarroyo, Manuel E.

doi:10.1016/j.jsb.2004.04.010

Cited by 11 publications

(9 citation statements)

References 33 publications

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“…H-bonds’ essential role in protein structure and in immune responses has become evident, since T-cell epitopes’ total retro-inversion ( d -aa) has been seen to have very low MHC binding capability and this was non-immunogenic [ 223 ]. We have found that specifically replacing l -aa with d -aa in MSP-1-derived HABP 1513 binding motif did not reduce its binding activity, although its secondary structure became distorted, and that d -analogues were less suitable for T-cell stimulation [ 224 , 225 , 226 ]. By contrast, some d -aa replacements (one at a time) in MSP-1-derived HABP 1585 produce d -analogues having improved resistance against proteolytic degradation and higher binding activity than that the cognate peptide.…”

Section: Chemical Features To Be Taken Into Account In Vaccine Devmentioning

confidence: 99%

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

et al. 2017

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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 falciparum conserved 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 π-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.

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Section: Chemical Features To Be Taken Into Account In Vaccine Devmentioning

confidence: 99%

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

et al. 2017

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“…Our approach is based on low-polymorphic sequences of Plasmodium which are then modified into immunological relevant motifs as well as strategically including lysosomal substrates to stimulate processing and presentation steps on vaccinated individuals. Therefore, we have analyzed and produced representative modified immunogens based on a number of native sequences belonging to different stages of Plasmodium which upon vaccination of animal models have proven to be effective against malaria infection and parasite clearance [41][42][43].…”

Section: New Modified Vaccine Components Containing Non-natural Elemementioning

confidence: 99%

The Next Vaccine Generation Against Malaria: Structurally Modulated Plasmodium Antigens

Lozano¹

2016

Current Topics in Malaria

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Challenges for obtaining more effective malaria vaccines depend on precise selection of antigenic motifs and understanding the complexity of Plasmodium spp. life cycle. Naturally expressed antigens are characterized for being weak immunogenic when tested as vaccine components, thus these have to be strategically modified to render them immunogenic. A molecular clue in this pursuit is provided by the chemical peptide-bond processing by peptidases, which follows a multistep pathway including ephemeral high energy molecular complexes known as transition states. Thus, we have proposed non-natural peptide-bond isosteres as transition states mimetics, and therefore, stabilizing these high-energy states with site-directed designed immunomimetics have demonstrated being a rational approach for stimulating antibody populations harboring multiple functional capacities. Therefore, peptide-bond substitutes constitute a coherent pathway towards obtaining selected immuno-active compounds from specific plasmodial molecular objectives. Chemical strategies for synthesizing peptido-mimetics and antimalarial selected trials lead us to assess a number of peptide-bond substitutes for obtaining immuno-active and structurally defined molecules. Plasmodium antigens expressed on merozoite, sporozoite and gametocyte stages have been selected as targets and subsequently modified based on the presence of either a high-binding motif or a potential HLA-reading frame. This new family of immuno-mimetics is and efficient neutralizing antibody inducers when tested in in vitro and in vivo experiments, thus representing a new generation of malaria vaccine components.

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“…reversal of the direction of the amide bond, has been successfully incorporated to many bioactive peptides [16][17][18][19][20][21][22][23][24][25]. Furthermore, the retroinverso amide bonds are also relevant in polymer science, since several families of well-studied synthetic polyamides involve a retro-inverso glycine residue as a part of their chemical repeating unit [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

“…The increasing apparition of studies devoted to design new classes of peptidomimetics with biological activity using retro-inverso modifications of the amide bond indicates a renewed interest in this field [16][17][18][19][20][21][22][23][24][25]. Therefore, the development of reliable force-field parameters to perform MM simulations of these biomolecules is highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Force-field parametrization of retro-inverso modified residues: Development of torsional and electrostatic parameters

Curcó

Rodríguez-Ropero

Alemán

2006

J Comput Aided Mol Des

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Torsional and the electrostatic parameters for molecular mechanics studies of retro-inverso modified peptides have been developed using quantum mechanical calculations. The resulting parameters have been compared with those calculated for conventional peptides. Rotational profiles, which were obtained spanning the corresponding dihedral angle, were corrected by removing the energy contributions associated to changes in interactions different from torsion under study. For this purpose, the torsional energy associated to each point of the profiles was estimated as the corresponding quantum mechanical energy minus the bonding and nonbonding energy contributions produced by the perturbations that the variation of the spanned dihedral angle causes in the bond distances, bond angles and the other dihedral angles. These energies were calculated using force-field expressions. The corrected profiles were fitted to a three-term Fourier expansion to derive the torsional parameters. Atomic charges for retro-inverso modified residues were derived from the rigorously calculated quantum mechanical electrostatic potential. Furthermore, the reliability of electrostatic models based on geometry-dependent charges and fixed charges has been examined.

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Mapping the anatomy of a Plasmodium falciparum MSP-1 epitope using pseudopeptide-induced mono- and polyclonal antibodies and CD and NMR conformation analysis

Cited by 11 publications

References 33 publications

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

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

The Next Vaccine Generation Against Malaria: Structurally Modulated Plasmodium Antigens

Force-field parametrization of retro-inverso modified residues: Development of torsional and electrostatic parameters

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