Antigenicity of Polypeptides (Poly Alpha Amino Acids)

Abstract

In continuation of studies to delineate some of the criteria for immunogenicity of synthetic random polymers of a-amino acids, we have investigated the contribution of the optical configuration of the amino acids. It was hoped that by studying the immunogenicity in several species of a variety of random terpolymers containing only D-a-amino acids or mixtures of D-and L-a-amino acids, some definite conclusions could be reached concerning the role of optical configuration in immunogenicity. Previously, we reported that two polymers consisting only of the D-a-amino acids, glutamic acid, alanine, and tyrosine (G60A40, G6oA30T10) 1 were not immunogenic in rabbits or guinea pigs (1), whereas the "isomeric" polymers of L-amino acids were effective immunogens (2, 3). Moreover, the polymer G60Aa0Ti0, made of I)-amino acids, could not act as a carrier in guinea pigs for the haptene specificity of arsanilic acid (4). The polymers employed in this study were optical variations of those previously shown to be immunogenic when made of L-a-amino acids. The findings on immunogenicity will be presented here and the immunochemical relationships of the polymers will be the subject of another publication. Materials and MethodsAntigens.--Random copolymers were prepared by the polymerization of the appropriate N-carboxy-a-amino acids anhydride of the configuration indicated in Table I, by methods referred to previously (1-5). The average molecular weights were obtained from viscosity measurements as well as from measurements with the analytical ultracentrifuge. 2 Some typica] sedimentation patterns of the preparations are shown in Fig. 1.

Biological weapons

“…This may be due to its repeating negative charge, its lack of L-amino acids and its unconventional peptide bonds [105]. Poor immunogenicity is consistent with the T-independent nature of bacterial polyanionic capsules [106,107].…”

“…Additionally, combining PA and FIS elicited better protection against fully virulent strains than either PA or FIS by itself. Glomski et al found that FIS could protect mice against a pXO1-negative spore challenge, and that this immunity was antibody independent [105]. Finally, an exosporium glycoprotein, BclA, has proven to be highly immunogenic [97] and might contribute to protection [42].…”

Carbunco. Prevención de la enfermedad

“…Su poca capacidad inmunogénica se debe a su estructura química y a la carga negativa que posee, lo que determina que se comporte, prácti-camente, como un antígeno T-independiente (Chabot et al, 2004;Maurer et al, 1965;Schneerson et al, 2003;Wang et al, 2004).…”

Role of the Protective Antigen Octamer in the Molecular Mechanism of Anthrax Lethal Toxin Stabilization in Plasma

“…Long, linear γ-DPGA chains (~50 kDa) can be isolated from vegetative B. anthracis grown in vivo 38. For B. anthracis , the genes responsible for producing the γ-DPGA polymer,32 anchoring it to the peptidoglycan cell wall,35 and cleaving it into smaller dissociable fragments,33-36 augment its virulence perhaps through a variety of mechanisms, namely allowing the bacillus to resist complement33,39 and phagocytosis 36. Interestingly, during infection lower-molecular-weight capsular fragments (L-capsule) are released from the bacillus by the hydrolytic enzyme dep, or capD 33-36.…”