Direct interaction rescue

The various modalities in which proteins are presented on the display vector are illustrated in Fig. 3 with respect to the association of monomers, heterodimers, and particularly for antibodies, the Fab, scFv and diabody display (see Refs. 38 and 39 for reviews). The direct interaction rescue system is treated separately below. 

Gramatikoff K, Georgiev O, Schaffner W, Direct interaction rescue, a novel filamentous phage technique to study protein-protein interactions, Nucleic. Acids. Res., 22 5761-5762, 1994. 

Recently, in an approach to explain the diverse actions of polyphenols, Howitz et al. suggested that the antiproliferative and oncosuppressive properties of resveratrol might be due to a mechanism that mimics caloric restriction and lifespan extension, and involves the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD) -dependent acety-lases (Howitz et al. 2003). More specifically, resveratrol was found to directly interact with SIRTl deacetylase, resulting in decreased acetylation of p53, increased DNA stability, and finally cell survival. Redox formation was implicated in the inhibition of histone deacetylase (HDAC) activity, leading to a chronic inflammatory-like response (Rahman et al. 2004). In this respect, resveratrol is a promising agent in the reversal of oxidative stress and rescue of mutant phenotypes. 

T) Do direct chemical interactions occur between rescue agents and platinum compounds (such as the drugs cisplatin and carboplatin transpla-tin), and between the relevant model compounds (such as Ptn(dien), or perhaps the kinetically faster reacting Pd11 compounds) Which interaction products are formed in vivo (structure, kinetics) This topic has been largely neglected in the literature. 

The Gl ribozyme reaction depends on the presence of divalent metal ions but as indicated above, the binding of these ions plays multiple roles that include folding and enhancing substrate binding affinities (59). The rate of the chemical step is Mg(2- -) dependent, but these data do not distinguish between direct or indirect roles, or a combination of both. As indicated above, distinguishing active site metal ions from what has been referred to as the sea of other functionally important metal ion interactions presents a considerable challenge. For the GI ribozyme and other catalytic RNAs, site-specific evidence for active site metal interactions comes primarily from analyses of thiophilic metal ion rescue of phosphorothioate and other substrate modifications (e.g.. References 60 and 61). These analyses rely on the fact that substitution of a substrate phosphate by a phosphorothioate weakens the affinity of coordinated Mg(2- -) ions... 

---