Targeting Tumor Markers with Antisense Peptides: An Example of Human Prostate Specific Antigen

Abstract

The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense–antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.

Antisense Peptide Technology for Diagnostic Tests and Bioengineering Research

“…The concept of sense and antisense (i.e., complementary) peptide interaction was developed in the early 1980s by Root-Bernstein, Biro, Blalock, Mekler, Siemion, and others [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. First, it was theoretically assumed and later empirically observed that peptides consisting of amino acids specified by sense and antisense sequences interact with higher probability and affinity than randomly selected peptides (Tables 1 and 2, Figure 1).…”

“…Sense peptides are essential and specific parts of viral and other proteins that elicit normal and pathologic immune responses [6][7][8][9]14,[19][20][21]. Using antisense peptide technology, they could be utilized to derive targeted tests for different antibody (Ab), hormone, growth factor, or cell subpopulations [4][5][6][7][8][9]13,14,[17][18][19][20][21][22][23].…”

“…Sense peptides are essential and specific parts of viral and other proteins that elicit normal and pathologic immune responses [6][7][8][9]14,[19][20][21]. Using antisense peptide technology, they could be utilized to derive targeted tests for different antibody (Ab), hormone, growth factor, or cell subpopulations [4][5][6][7][8][9]13,14,[17][18][19][20][21][22][23]. The potential of antisense peptides is twofold: 1. as future diagnostic tests targeting protein epitopes or paratopes of interest, or 2. as future therapeutic agents that target specific parts of antigens to selectively modify host immune response (e.g., an antisense peptide may disrupt or modify different factors like virulence, replication or host defense) [6][7][8][9]13,14,[18][19][20][21].…”

“…Using antisense peptide technology, they could be utilized to derive targeted tests for different antibody (Ab), hormone, growth factor, or cell subpopulations [4][5][6][7][8][9]13,14,[17][18][19][20][21][22][23]. The potential of antisense peptides is twofold: 1. as future diagnostic tests targeting protein epitopes or paratopes of interest, or 2. as future therapeutic agents that target specific parts of antigens to selectively modify host immune response (e.g., an antisense peptide may disrupt or modify different factors like virulence, replication or host defense) [6][7][8][9]13,14,[18][19][20][21]. Consequently, sense-antisense peptide interactions may serve as a useful starting point for: 1. the development of biochemical assays for the evaluation of the immune response, and 2. modeling and design of new peptide binders for specific proteins and their receptors.…”

“…Consequently, sense-antisense peptide interactions may serve as a useful starting point for: 1. the development of biochemical assays for the evaluation of the immune response, and 2. modeling and design of new peptide binders for specific proteins and their receptors. Sense peptides are essential and specific parts of viral and other proteins that elicit normal and pathologic immune responses [6][7][8][9]14,[19][20][21]. Using antisense peptide technology, they could be utilized to derive targeted tests for different antibody (Ab), hormone, growth factor, or cell subpopulations [4][5][6][7][8][9]13,14,[17][18][19][20][21][22][23].…”