Peptide homodimers

Here, U represents unfolded bZIP monomer, A2 represents coiled-coil homodimer, O represents duplex DNA, and A2O represents the DNA peptide homodimer complex. Ki represents the dissociation constant of the peptide homodimer and K2 represents the dissociation constant of the complex of this homodimer and DNA. For this case, the following equilibrium and mass conservation equations hold ... 

Under our experimental conditions, the total peptide concentration, Atotal. exceeds the total DNA concentration (<50 pM) by a factor of at least 10. As a result, the term [A2O] in equation (3) is small compared with Atotal and can be ignored. Equation 3 is simplified further by the consideration that the values of for the peptide homodimers studied here are also greater than Atotal- The value of Ki for GCN4p, a peptide that differs from ggg by four residues at the amino terminus, is approximately 5 iM under experimental conditions almost identical to those used here we assume that the K for ggg and gcg are similar based on their similar Tm values (67 versus 66 7 °C, respectively). If so, at the highest concentration of ggg or gcg used (30 nM), the concentration of homo-... 

Filizola, M. and Weinstein, H. (2002) Structural models for dimerization of G protein coupled receptors the opioid receptor homodimers. Biopolymers (Peptide Sci.) 66, 317-325. 

Fatty acid synthase in vertebrates consists of two identical peptide chains—i. e., it is a homodimer. Each of the two peptide chains, which are shown here as hemispheres, catalyzes all seven of the partial reactions required to synthesize palmitate. The spatial compression of several successive reactions into a single multifunctional enzyme has advantages in comparison with separate enzymes. Competing reactions are prevented, the individual reactions proceed in a coordinated way as if on a production line, and due to low diffusion losses they are particularly ef dent. 

For the synthesis of heterodimeric cystine peptides where two different peptide chains are cross-linked by a disulfide bridge random co-oxidation of the two chains besides producing the heterodimer leads in the optimal case to the additional two homodimers in statistical distribution. Therefore, chemical control of the disulfide bridging via site-directed disulfide formation techniques is required since a thermodynamic control for generation of heterodimers is extremely difficult to achieve (see Section 6.1.5). 

These early studies clearly revealed the inherent problems of the chemistry for site-directed formation of unsymmetrical disulfides that has to avoid formation of homodimers. These can result from (i) slow rates of activation of the cysteine peptide, (ii) disproportionation of the activated cysteine species, (in) weak activation and thus slow thiolysis by the second cysteine component and thus its oxidation to the homodimer as well as thiol/ disulfide exchange reactions on the unsymmetrical disulfide present in the reaction media. The latter side reactions are partly controlled by operating in degassed argon-saturated buffers or in organic solvents and preferably under acidic conditions where thiol/disulfide exchange reactions on the nonactivated disulfides, i.e. on the target unsymmetrical cystine peptide occurs at slow rates. 

Oxidation of mono-cysteine peptides to the dimer is a straightforward reaction that can produce only the desired product. In the case of bis-cysteine peptides statistically the oxidation leads to the homodimers in parallel and antiparallel orientation as well as to the disulfide-bridged monomer and oligomers. When the two cysteine residues are placed in the adjacent position formation of homodimers is highly favored over the cyclic monomer (Section 6.1.5.1) and the product distribution depends strongly on the peptide concentration. Such a type of intermolecular disulfide bridging is present in bovine seminal ribonuclease, where an antiparallel alignment occurs at the interface of the dimer. 97 ... 

Structure-function studies of IFN-y carried out using the synthetic peptide approach and site-specific antibodies indicated that both the N- and C-terminal regions of the protein were not only functionally important, but also accessible at the surface of the molecule. The x-ray crystal structure of human IFN-y has been determined and reveals that in the IFN-y homodimer both the N- and the... 

Coil-Ser A Peptide Designed as Parallel Homodimer that Forms an Up-Up-Down Homotrimer (1990)... 

FIGURE 7.14. Schematic illustration of the inhibition of HIV-1 protease homodimer by amphiphiles that tether two peptides mimicking the interface of the protease. Optimization of the potency of the inhibitor is achieved by varying the residues on the amphiphiles, as shown below die illustration. 

Scheme 1. Reduction of homodimer peptide linked via a disulfide bridge with dithio-threitol (DTT) and alkylation of the resulting thiol groups of both cysteines with either acrylamide (upper reaction) or iodoacetamide (lower reaction).

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