Protection against malaria induced by chirally modified Plasmodium falciparum’s MSP-142 pseudopeptides

What is Hidden Behind Peptide Bond Restriction and α-Carbon Asymmetry of Conserved Antigens? Peptide Bond Isosters and Chirally Transformed Pseudopeptides as Novel Elements for Synthetic Vaccines and Therapeutic Agents Against Malaria

“…This data was more compatible with naturally infective conditions, since immunisations with this surrogate induced immune protection against a heavy infection induced by mosquito bite, as happens in hyper endemic malarial areas such as sub-Saharan African countries. In vitro HLA-DR *1-binding data has demonstrated that most D-substitutions in the all-L 1585 peptide specifically bound the HLA-DR 1*1101 allele by increasing binding from 27 ± 3% of parent all-L 1585 peptide to 91 ± 8% for partial D-substitution in P 7 residue [82]. Fig.…”

The Next Vaccine Generation Against Malaria: Structurally Modulated Plasmodium Antigens

“…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].…”

“…Similarly, CD profile for the L-native sequence compared with that of the Retro-inverso analogue (green line), behave as mirror images of each other bearing in mind that both were made with only l-amino acids, but having opposite peptide backbone orientation. [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] peptide. The native sequence is represented in capital letters for l-amino acids, D-enantiomer represented by lowercase letters purple highlighted, Retro-sequence is constituted by d-amino acids in lowercase letters blue highlighted and the so-named Retro-inverso peptidomimetic is confirmed by l-amino acids green highlighted.…”

“…The native sequence is represented in capital letters for l-amino acids, D-enantiomer represented by lowercase letters purple highlighted, Retro-sequence is constituted by d-amino acids in lowercase letters blue highlighted and the so-named Retro-inverso peptidomimetic is confirmed by l-amino acids green highlighted. (B) Circular dichroism secondary structure patterns for PfMSP1 [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] peptido-mimetics. Used color code was black line for the native sequence, purple for its D-enantiomer, blue line for the Retro-analogue and green line for the Retroinverso peptido-mimetic.…”

“…Used color code was black line for the native sequence, purple for its D-enantiomer, blue line for the Retro-analogue and green line for the Retroinverso peptido-mimetic. Competition ELISA was used for the PfMSP1 [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] peptide mapping with monoclonal antibodies coded Ig-αψ-437( 52 V-L 53 ) and Ig-αψ-439( 51 M-V 52 ) as shown in (C) and (D), respectively. IC50 μM values represent the average of data obtained in triplicate.…”