Anti-tumor peptides

The following chapters will present applications of the ab initio method to different biochemical systems, such as amino acids, peptides, and anti-tumor drugs. 

Yamaguchi S, Tatsumi T, Takehara T et al (2010) EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. Cancer Immunol Immunother 59 759-767... 

We first describe the NMR parameters for the duplex to strand transition of the synthetic DNA poly(dA-dT) (18) with occasional reference to poly(dA-dU) (24) and poly(dA- brdU) and the corresponding synthetic RNA poly(A-U) (24). This is followed by a comparison of the NMR parameters of the synthetic DNA in the presence of 1 M Na ion and 1 M tetramethylammonium ion in an attempt to investigate the effect of counterion on the conformation and stability of DNA. We next outline structural and dynamical aspects of the complexes of poly(dA-dT) with the mutagen proflavine (25) and the anti-tumor agent daunomycin (26) which intercalate between base pairs and the peptide antibiotic netropsin (27) which binds in the groove of DNA. 

Peptide boronates are much more potent proteasome inhibitors than aldehydes [43[. Boronate-proteasome adducts have much more slower dissociation rates than proteasome-aldehyde adducts, and although boronates are considered reversible inhibitors, the inhibition is practically irreversible over a period of hours. In addition, PS-341 inhibits serine proteases 1000-fold weaker than it does the proteasome [43[. This combination of potency, selectivity and metabolic stability makes the peptide boronates better drug candidates than other classes of proteasome inhibitors. In vitro and mouse xenograft studies of PS-341 have shown anti-tumor activity in a variety of tumor types. DFLB and PS-273 are usefiil fluorescent active site probes binding of these inhibitors enhances the fluorescence of their environment-sensitive dansyl and naphthyl moieties [44]. 

AMPs can act as adjuvants for adaptive immune responses, enhancing specific and protective responses. LL-37 [200], cathelin-related antimicrobial peptide (CRAMP) [189] and mouse BD-2 [201] enhanced antigen-specific humoral and cellular immune responses, and induced protective anti-tumor immunity in some conditions [200]. It has been suggested that even low doses of AMPs can influence immune responses, since LL-37 has a synergistic activity with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-ip [155,196]. 

Recently it was demonstrated that transfection of tumor cells with an antitumor peptide induced a protective immune reponse. Inoculation of mice with murine BD-2-transfected leukemia cells enhanced cytotoxic T lymphoc)des (CTL) and natural killer (NK) anti-tumor activity, with augmented IL-12 and IFN-y production. Animals vaccinated with transfected cells were protected against a challenge with parental cells (50% protection) and the vaccination generated leukemia-specific memory CTL [210]. 

A few other anti-angiogenic peptides have been studied and their anti-tumor properties evaluated in vivo. The C-terminal segment of platelet factor 4, conserves a potent anti-angiogenic... 

Peptides eliciting anti-tumor immune responses... 

Another strategy aimed at inducing an immune response against TAAs is the application of peptides thereof with an immunogenic potential [92]. This soluble, rather than cell-based, material has been used to stimulate anti-tumor T cells and to destroy cells that present the peptide epitopes on their cell surface [93-95]. This therapy has several advantages, as peptide-based vac-... 

A. Gaowa, T. Horibe, M. Kohno, K. Sato, H. Harada, M. Hiraoka, Y. Tabata, and K. Kawakami, Combination of hybrid peptide with biodegradable gelatin hydrogel for controlled release and enhancement of anti-tumor activity in vivo, /. Control. Release, 176, 1-7, 2014. 

Anlezark et al. (1) followed shortly thereafter with a report on the purification of a classical nitroreductase from Escherichia coli B. The enzyme is an FMN-containing flavo-protein of approximately 24 kDa that uses NAD(P)H as the electron donor. The enzyme specifically reduces the anti-tumor agent CB1954 (5-[aziridin-l-yl]-2,4-dinitrobenzamide) to the 4-hydroxylamino derivative (Fig. 4). The isoelectric point of the protein is 5.1 which is similar to the values of 5.3 and 5.6 calculated for the Salmonella and Enterobacter enzymes, respectively. The sequence of 31 amino acids at the N-terminus of the E. coli enzyme was determined, and a further 41 residues were obtained from a peptide generated... 

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