Cationic residues

As such, the magainins provide a useful initial target for peptoid-based peptido-mimetic efforts. Since the helical structure and sequence patterning of these peptides seem primarily responsible for their antibacterial activity and specificity, it is conceivable that an appropriately designed, non-peptide helix should be capable of these same activities. As previously described (Section 1.6.2), peptoids have been shown to form remarkably stable hehces, with physical characterishcs similar to those of peptide polyprohne type-I hehces (e.g. cis-amide bonds, three residues per helical turn, and 6A pitch). A faciaUy amphipathic peptoid helix design, based on the magainin structural motif, would therefore incorporate cationic residues, hydrophobic aromatic residues, and hydrophobic aliphathic residues with threefold sequence periodicity. 

Both the 3i4- and 2.5i2-helical backbones have been found suitable for the design of antimicrobial /9-peptides. In order to cluster polar residues on one face of the helix, amphiphilic 3i4-helical /9-peptides have been constructed from hydro-phobic-cationic-hydrophobic or hydrophobic-hydrophobic-cationic residue triads... 

The amino acid sequences of haptides comprise hydrophobic and cationic residues with a net charge of +4 to +5 per 19 to 21 amino acids. It was proposed that haptides could be attracted to the anionic liposomes as well as the anionic cell membrane and that the hydrophobic properties of the haptide facilitate membrane translocation (106). Haptide uptake was reported to be energy independent, occurring at 4°C. The advantage of this peptide compared to CPP such as TAT and Antp, is that, unlike the virus-derived peptides, the haptides are not recognized as foreign antigens and do not induce cell transformation (106). However, haptides have also been found to accelerate fibrin clot formation and lack cell specificity (106). 

The scorpion a-toxins have been shown to bind to site 3 on the voltage-gated sodium channel [24,27,42]. These polypeptides contain up to 70 residues crosslinked by four disulfide bonds, but show no sequence similarity to the anemone polypeptides. Possible structural similarities have been discussed [24], and in a theoretical model of the anemone toxin Bg II, some of the cationic residues were in similar locations to those in the crystal structure of the scorpion toxin Aah II [26]. 

Gallagher MJ, Blumenthal KM. Importance of the unique cationic residues arginine-12 and lysine-49 in the function of the cardiotonic polypeptide anthopleurin-B. J Biol Chem 1994 269 254-259. 

Lysine is the principal cationic residue in caseins, with lesser amounts of arginine and histidine (pKa 6). 

A detailed study of the kinetics of the Lys 41 reaction by Murdock et al. (124) indicates that the pK of Lys 41 is 8.8 0.1. This value is about 1.4 pH units lower than that for the usual t-amino groups and would account for the apparent enhanced reactivity at lower pH. The second-order rate constant corrected to the free base form is within a factor of 2 of that derived from data on simple peptides. A strongly cationic center was inferred as the reason for this low pXa. In the X-ray structure a number of cationic residues are, in fact, close by, especially Arg 39. 

The Influence of the Ionic Strength on the Clotting Time. We have seen that between I = 0.03 and 0.5 an increase of the ionic strength chiefly brings about a decrease of the rate of proteolysis. We shall now present a simple argument to explain the effect of salt and to show the importance of the cluster of cationic residues around the labile Phe-Met bond in -casein (5) in stabilizing the ES-complex. If the latter is identified with Bronsted s activated complex (13), one has for the rate of proteolysis... 

Other peptides containing histidines listed in Table 16.2, such as those of the histatin family (antimicrobial peptides), Sea Urchin (B18) and LAH4, strongly interact with phospholipid membranes and destabilize them. LAH4, which does not contain other cationic residues, exhibits a-helix and is more active in an acidic medium. These peptides could be putative endosome disrupting helpers that have not yet been used for polyfection. 

Diazo Components With Two Different Cationic Residues. Mono- and disazo dyes have been prepared in which the diazo compound carries at least two different basic and/or cationic groups.Reaction of 2,4- or 2,5-diaminobenzene sulfonic acids with 2-chloro-l,3,5-triazines that are substituted in positions 4 and 6 by aminoalk-ylamines and cyclic ammonium alkylamines, respectively, leads to diazo compo-... 

A further means to introduce different basic and/or cationic residues into a dye has been developed by combining diazo and coupling components that each carry different basic or cationic groups. They are synthesized according to the procedures described above. Dyes have been prepared that color paper in hues ranging from orange [135], e g., 47, to red [136-138], e.g., 48, to black [136], e.g., 49. 

An additional characteristic of inverse substrates is also shown in Fig. 4. The acyl enzyme formed from the inverse substrate lacks a site-specific cationic residue with... 

In Eqs. (51) and (52), a is comparable with a cooperative coefficient, representing the basic bonding constant. The values of A, B, a and ft are complied in Table 22. In the range of the chain lengths of these oligocations, the standard free energy change of complex formation decreases by about 0.6 kcal/mol upon the addition of one cationic residue. The difference of/3 (about 1.6 kcal/ mol) between two different types of cations may be due to the variation of the hydrophobidties between benzyl and methyl residues. 

TABLE 14.2. Cationic residues in the amino acid sequence of lysozyme and cytochrome c [19]. 

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