Specificity multispecificity

T., and Inui, K.-L (2001) Multispecific substrate recognition of kidney-specific organic anion transporters OAT-Kl and OAT-K2. The Journal of Pharmacology and Experimental, Therapeutics 299, 261-267. 

A more refined definition of promiscuity should include a quantitative measure for the degree and magnitude of promiscuity. The degree of promiscuity refers to the level to which enzyme specificity is breached (or the degree of multispecificity for enzymes that react with a broad range of different substrates). Namely, how different are the native and promiscuous functions. The magnitude of promiscuity refers to the kinetic parameters for the promiscuous activity relative to the native one. 

Almost all cases of substrate ambiguity and multispecificity (as defined in Section 8.03.3) are manifested in differences in the 4th digit. Examples for multispecific, or broad-specificity enzymes include sulfotransferases and GSTs (Table 1, entries 1, 2). 

No single system can be universal in showing uf the herbicidal potential of all compounds. No in vitro system using cells or mini-plants represents all tissues and all species. Herbicides can be tissue specific and species selective and different herbicides act at different rates. This requires that any universal pre-screen has to be multispecific, multi-tissue and multi-time. Many of the factors for consideration in developing such screens may superficially seem mundane or clearly apparent. Based on failures, this is only so in retrospect. 

RNA aptamer specifically binding and inhibiting the activity of the catalytic ricin A-chain (RTA) has been selected [57]. Initially 80 nucleotides long, it has been shortened to 31-nucleotide aptamer that contained all sequences and structures necessary for interacting with RTA. Inhibition properties of this aptamer exceeded known ricin inhibitors. This aptamer along with others was used to develop a multispecific sensor. Aptamers were immobilized on beads, introduced into micromachined chips on the electronic tongue sensor array, and used for the detection and quantification of proteins. The lowest detected ricin concentration using this sensor was 1 pM (320 ng/mL) [58]. 

In addition to target-associated toxicides, intrinsic toxicides associated with mAb modalities may be predicted based on the specific construct. As a class, mAb-based therapies include whole antibodies, antibody fragments, Fc-modified peptides and proteins, bi-/multispecific consducts, ADCs, effector-modified antibodies, and many other engineered... 

Evidence that certain naturally occurring antibodies of the nurse shark may be multispecific was presented by Rudikoff et al. (107). Antibody specifically purified by absorption to, and elution from a Dnp-coiyugate, agglutinated sheep and pigeon erythrocytes and bound guanosine monophosphate. 

If combining sites are indeed multispecific, this could greatly reduce the number of structural genes needed to encode the library of specificities available to an individual animal. A clearer picture of the nature of the active site, and in particular as to its size, is emerging from X-ray crystallographic investigations. This should indicate whether this type of... 

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