Investigations into the cross‐reactivity of rabbit antibodies raised against nonhomologous pairs of synthetic peptides derived from HIV‐1 gp120 proteins

Abstract

The immunological cross‐reactivity of several peptides with specific pattern‐property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV‐1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross‐react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure‐function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico‐chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side‐chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic α‐helices and β‐sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gpl60/120 glycoproteins from a range of HIV‐1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gpl20. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV‐1 proteins. These nonhomologous synthetic peptides induced cross‐reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV‐1 ENV gpl20‐related proteins, as determined by enzyme‐linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross‐reactivity and molecular biomimicry in the development of peptide‐based vaccines directed against viral or bacterial pathogens.

Quantum Foundations of Resonant Recognition Model

“…As was shown in our previous studies of FGF peptidic antagonists [1,11] and HIV envelope agonists [12,13] such de novo designed peptides express the desired biological function.…”

Development of new computational amino acid parameters for protein structure/function analysis within the resonant recognition model

“…A number of amino acid indices (402 have been published up to now [9]) have been found to correlate in some way with the biological activity of the whole protein. Previous investigations [1][2][3][4][5] have shown that the best correlation can be achieved with parameters, which are related to the energy of delocalised electrons of each amino acid. These findings can be explained by the fact that the electrons delocalised from the particular amino acid have the strongest impact on the electronic distribution of the whole protein.…”

“…Through an extensive study, the RRM has reached a fundamental conclusion: one RRM characteristic frequency characterizes one particular biological function or interaction [2,3]. Once the RRM characteristic frequency for a particular biological function or interaction has been determined, it is possible to identify then the individual amino acids so called "hot spots", or domains that contribute mostly to the characteristic frequency and thus to protein's biological function as well [3,4]. The RRM is based on the representation of the protein primary structure as a numerical series by assigning to each amino acid a physical parameter value relevant to the protein's biological activity.…”

Analysis of HIV proteins using DSP techniques

“…The RRM analysis showed that these regions share the same characteristic frequency f1 (as gp160env proteins), but they also have their own more prominent characteristic at frequency f2=0.219+0.022 [1][2][3]12,13,15].…”

“…Only one common frequency component for all analysed isolates was obtained as prominent peak at frequency f1=0.185+0.001 (signal-to-noise=484) in the crosspectral function (Fig.1). According to RRM concepts, it can be proposed that this frequency characterises the common biological behavior of all analysed proteins [1][2][3][4]12,13,15]. Figure 1 Cross-spectral function of gp160 env proteins from 19 different isolates revealing the characteristic frequency at f1=0.1855.…”