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Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Curtidor, Hernando; Reyes, César; Bermúdez, Adriana; Vanegas, Magnolia; Varela, Yahson; Patarrollo, Manuel Elkin (2017)

Abstract: 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 ...
Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections

Araujo, Zaida; de Waard, Jacobus H.; Camargo, Milena; Lopez Ramos, Juan Ernesto; Fernández de Larrea, Carlos; Vanegas, Magnolia; Patarroyo, Manuel-Alfonso (2022)

Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for efective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests ...
p-Methoxyphenol: A potent and effective scavenger for solid-phase peptide synthesis

Samacá, Jhoan; Velandia Bautista, Erika; Tabares, Luisa; Escamilla, Luis; Vanegas, Magnolia; Patarroyo, Manuel Elkin (2020)

During the final step of t-Boc/Bzl, solid-phase peptide synthesis (SPPS)-protecting groups from amino acids (aa) side chains must be removed from the target peptides during cleavage from the solid support. These reaction ...
Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Lambraño, Jennifer; Curtidor, Hernando; Avendaño, Catalina; Díaz Arévalo, Diana; Roa, Leonardo; Vanegas, Magnolia; Patarroyo, Manuel Elkin; Patarroyo, Manuel A. (2019)

Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that 219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. ...
Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

Bermudez, Adriana; Alba, Martha p.; Vanegas, Magnolia; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin (2018)

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types ...
Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines

Patarroyo, Manuel-Elkin; Bermudez, Adriana; Alba, Martha patricia; Patarroyo, Manuel-Alfonso; Suárez, Carlos; Aza-Conde, Jorge; Moreno-Vranich, Armando; Vanegas, Magnolia (2022)

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is ...

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Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective
...
Curtidor, Hernando | 2017

Abstract: 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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Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections
...
Araujo, Zaida | 2022

Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for efective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests to distinguish between ATB and LTBI has remained challenging. The present study was aimed to demonstrate the usefulness of the serological response to synthetic peptides from Mycobacterium tuberculosis (Mtb) antigens for discrimination between ATB and LTBI in Warao Amerindians. Serum IgG antibody levels were measured by the indirect ELISA assay using 22 designed and synthesized peptides derived from immunogenic Mtb ESAT-6 and Ag85A proteins. A total of 211 adult Warao Amerindians were included; cases with active TB (ATB, n=75), latent TB infection (LTBI, n=85) and non-infected (NI, n=51). The approach’s diagnostic information was compared using receiver operating characteristic (ROC) curves. For ATB diagnostic performance between ATB and NI; ESAT-6; P-12037 had 100% of sensitivity (AUC=0.812; 0.733 to 0.891 95% CI); and Ag85A; P-10997 had 100% of specifcity (AUC=0.691; 0.597 to 0.785 95% CI); and ATB and LTBI; Ag85A; P-29878 had 100% of sensitivity (AUC=0.741; 0.666–0.817 95% CI), and P-29879 had 99% of specifcity (AUC=0.679; 0.593–0.765 95% CI). While that ESAT-6 P-12037 also allowed diferentiation between LTBI and NI or healthy ones. It had 98.8% of sensitivity and 98.0% of specifcity (AUC=0.640; 0.545–0.735 95% CI). The potential of combination-antigen immunoassays with peptides could discriminate between Warao Amerindians with ATB, LTBI and NI. Further validation of this approach could lead to developing a complementary tool for rapid diagnosis of TB infections.

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p-Methoxyphenol: A potent and effective scavenger for solid-phase peptide synthesis
...
Samacá, Jhoan | 2020

During the final step of t-Boc/Bzl, solid-phase peptide synthesis (SPPS)-protecting groups from amino acids (aa) side chains must be removed from the target peptides during cleavage from the solid support. These reaction steps involve hydrolysis with hydrogen fluoride (HF) in the presence of a nucleophile (scavenger), whose function is to trap the carbocations produced during SN1-type reactions. Five peptide sequences were synthesised for evaluating p-methoxyphenol effectiveness as a potent scavenger. After the synthesis, the resin–peptide was then separated into two equal parts to be cleaved using two scavengers: conventional reactive p-cresol (reported in the literature as an effective acyl ion eliminator) and p-methoxyphenol (hypothesised as fulfilling the same functions as the routinely used scavenger). Detailed analysis of the electrostatic potential map (EPM) revealed similarities between these two nucleophiles, regarding net atomic charge, electron density distribution, and similar pKa values. Good scavenger efficacy was observed by chromatography and mass spectrometry results for the synthesised molecules, which revealed that p-methoxyphenol can be used as a potent scavenger during SPPS by t-Boc/Bzl strategy, as similar results were obtained using the conventional scavenger.

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Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model
...
Lambraño, Jennifer | 2019

Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that 219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. The disease cost the lives of more than 400,000 people, mainly in Africa. In spite of great efforts aimed at developing better prevention (i.e., a highly effective vaccine), diagnosis, and treatment methods for malaria, no efficient solution to this disease has been advanced to date. The Fundación Instituto de Inmunología de Colombia (FIDIC) has been developing studies aimed at furthering the search for vaccine candidates for controlling P. falciparum malaria. However, vaccine development involves safety and immunogenicity studies regarding their formulation in animal models before proceeding to clinical studies. The present work has thus been aimed at evaluating the safety and immunogenicity of a mixture of 23 chemically synthesised, modified peptides (immune protection-inducing protein structure (IMPIPS)) derived from different P. falciparum proteins. Single and repeat dose assays were thus used with male and female BALB/c mice which were immunised with the IMPIPS mixture. It was found that single and repeat dose immunisation with the IMPIPS mixture was safe, both locally and systemically. It was observed that the antibodies so stimulated recognised the parasite's native proteins and inhibited merozoite invasion of red blood cells in vitro when evaluating the humoral immune response induced by the IMPIPS mixture. Such results suggested that the IMPIPS peptide mixture could be a safe candidate to be tested during the next stage involved in developing an antimalarial vaccine, evaluating local safety, immunogenicity, and protection in a nonhuman primate model.

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Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components
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Bermudez, Adriana | 2018

The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

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Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines
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Patarroyo, Manuel-Elkin | 2022

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex’s stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes’ perfect fit into MHC-II human (HLADRβ̞1*) or Aotus (Aona DR) molecules. The enormous relevance of several amino acids’ physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRβ1* structures’ Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRβ1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids’ role and that of structures interfering with PPIIL formation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them

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Browsing by Author "Vanegas, Magnolia"

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective ﻿

Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections ﻿

p-Methoxyphenol: A potent and effective scavenger for solid-phase peptide synthesis ﻿

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model ﻿

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components ﻿

Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines ﻿

Envíos recientes

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections

p-Methoxyphenol: A potent and effective scavenger for solid-phase peptide synthesis

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines

Conserved binding regions provide the clue for peptide-based vaccine development: A chemical perspective

Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections

p-Methoxyphenol: A potent and effective scavenger for solid-phase peptide synthesis

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model

Specific β-turns precede PPIIL structures binding to allele-specific HLA-DRβ1* PBRs in fully-protective malaria vaccine components

Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines