Cationic peptides crystallization

FIGURE 2 Space-filling model of the dimeric opioid peptide biphalin as determined by a single crystal x-ray study [4]. The peptide cation co-crystallizes with a sulfate anion and several molecules of water. The illustration shows how the peptide interacts with the sulfate anion and one of the water molecules. 

A quite new type of antibiotic and one of the few naturally-occurring boron compounds is boromycin (86). Hydrolytic cleavage of D-valine with the M(7) hydroxides gave caesium and rubidium salts of this antibiotic, and crystal structure analysis established the formula as (XIIT). The rubidium ion is irregularly coordinated by eight oxygen atoms. Experiments with models showed that the cation site would be the natural place for the—NH3+ end of the D-valine residue, and the whole structure raises the possibility that transport of larger alkali metals is related to the N-ends of peptides and proteins. 

An analysis of metal binding to peptide carbonyl groups (Chakrabarti, 1990), mainly calcium ions in protein crystal structures, shows that the cations tend to lie in the peptide plane near the C=0 bond direction. Generally, this binding occurs in turns in proteins or in regions with no regular secondary structures. Ca---0 distances range from 2.2 to 2.5 A, and metal ions do not deviate by more than 35° from the peptide plane. Thus, metal ions in proteins do not, Chakrabarti observed, bind in lone-pair directions. 

Polymer membranes have also been explored as scaffolds for bio-mineralization. PMOXA-PDMS-PMOXA vesicles were loaded with phosphate anions. Alame-thicin, an ion channel peptide reconstituted in the vesicle membrane, allowed for cation (calcium) transport. After a certain incubation time, calcium phosphate crystals were seen inside the vesicles (Fig. 17), while no crystallization occurred in the outside medium [163],... 

The interaction between cyclic peptides and metal cations is closely related to their activities as antibiotics and to ion transport processes. An example of such interaction by a cyclic dipeptide is the complex formed by Li and cyc/o(Sar)2. The Li forms four Li" —O ligands (the length of which is near 1.92 A) with the C=0 groups of four independent cyc/o(Sar)2 molecules that surround the Li" in a tetrahedral array. The other C=0 of each dipeptide coordinates to another Li" to make an infinite two-dimensional network in the crystal (Takahashi et a/., 1977). 

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