Protein terminal group

A complete set of intermolecular potential functions has been developed for use in computer simulations of proteins in their native environment. Parameters have been reported for 25 peptide residues as well as the common neutral and charged terminal groups. The potential functions have the simple Coulomb plus Lennard-Jones form and are compatible with the widely used models for water, TIP4P, TIP3P and SPC. The parameters were obtained and tested primarily in conjunction with Monte Carlo statistical mechanics simulations of 36 pure organic liquids and numerous aqueous solutions of organic ions representative of subunits in the side chains and backbones of proteins... 

Proteolytic enzymes - hydrolyse proteins selectively, either on terminal groups (exopeptidases) or internal linkages (endopeptidases), eg... 

Dinitrofluorobenzene (86, X = F) is, because of its reactivity, much used for tagging the NH2 group of terminal amino-acids in protein end group analysis. Once it has reacted with the NH2 it is very difficult to remove again and will thus withstand the subsequent hydrolysis of the protein to its constituent amino-acids. 

Protein functional groups able to react with anhydrides include the oc-amines at the N-terminals, the s-amine of lysine side chains, cysteine sulfhydryl groups, the phenolate ion of tyrosine residues, and the imidazolyl ring of histidines. However, acylation of cysteine, tyrosine, and histidine side chains forms unstable complexes that are easily reversible to regenerate the original group. Only amine functionalities of proteins are stable to acylation with anhydride reagents (Fraenkel-Conrat, 1959 Smyth, 1967). 

The relative reactivity of a-haloacetates toward protein functional groups is sulfhydryl > imidazolyl > thioether > amine. Among halo derivatives the relative reactivity is I > Br > Cl > F, with fluorine being almost unreactive. The oc-haloacetamides have the same trend of relative reactivities, but will create a terminal amide group not a terminal carboxylate. 

Anderson, P.W., Pichichero, M.E., Stein, E.C., Porcelli, S., Betts, R.F., Connuck, D.M., Korones, D., Insel, R.A., Zahradnik, J.M., and Eby, R. (1989) Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen uniterminally coupled to the diphtheria protein CRMI97./. Immunol. 142, 2464-2468. 

Singh, P. (1998) Terminal groups in starburst dendrimers Activation and reactions with proteins. Bioconjugate Chem. 9, 54-63. 

Matta [37] used the conjoining of Aa residues to obtain the properties of the charge distributions of the proteins Leu- and Met-enkephalin that consist of five residues, in a study of the agonistic activity of the oripavine PEO and morphine. Assembly of the five residues with the required terminal groups resulted in net charges of +0.051 e and -0.043 e, respectively. 

In summary, dendrimers are a unique class of monodispersed synthetic molecules reminiscent of proteins or nucleic acids. If they can be functionalized to be soluble in water with appropriately charged terminal groups, they are generally ideal candidates for gel electrophoretic analyses. 

In a similar fashion, the Rotello group reported several protein-mediated assemblies of nanoparticles (Srivastava, Verma, et al. 2005 Verma et al. 2005). Unstable proteins such as chymotrypsin are readily denatured upon prolonged interaction with functionalized nanoparticles because of the exposure of proteins to the hydrophobic layer (Srivastava, Verma, et al. 2005). Addition of a hydrophilic portion to the monolayer by inserting a short tetraethylene glycol between the charged terminal group and hydro-phobic aliphatic chain circumvented this denaturation problem (Hong et al. 2004). 

Amino acids are attached to each other by peptide bonds. All a-amino and a-carboxyl groups participate in these bonds except the terminal groups on the protein. These are charged at physiologic pH. Sequences of amino acids in a peptide are read from the amino-terminal end to the carboxy-terminal end. 

The 3 -terminal group of three nucleotides, CCA, is invariant among all tRNA molecules and is labile, undergoing active removal and resynthesis. The rate of this turnover is sufficient to involve about 20% of the tRNA molecules of a cell per generation, but it is very much slower than the rate of participation of the tRNA molecules in protein synthesis. The physiological significance of end turnover is unknown.233 While this CCA sequence is encoded in bacterial tRNA genes, it is added in a separate reaction in eukaryotes.234... 

Most of these polymers have multi-functional character, which results in cross-linked heterogeneous products. In contrast, monomethoxy polyethylene glycol (PEG) presents only one reactive terminal group per polymer chain. Once PEGy-lated with these compounds, the protein acquires a brush-like shape, with the hydrophilic PEG chains extended from the protein to the solvent. 

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