Guanidiniocarbonyl pyrroles

Schmuck, C., Lex, J. (1999) Acetate binding within a supramolecular network formed by a guanidiniocarbonyl pyrrole cation in the solid state, Org. Lett. 3, 1253-1256. 

Schmuck, C. (2001) Self-assembly of 2-(guanidiniocarbonyl)-pyrrole-4-carboxylate in dimethyl sulfoxide an entropy driven oligomerisation, Tetrahedron 57, 3063-3067. 

We will demonstrate in this chapter our approach towards modular receptors for complexation of biologically relevant peptides in water. A new binding motif for carboxylates, the guanidiniocarbonyl pyrroles, has been designed this enables the formation of stable ion pairs even in aqueous solvents. By a stepwise elongation of this binding motif with additional interaction sites receptors are obtained that bind not only carboxylates but also single amino acids, both side-chain- and ste-reoselectively, and even tetrapeptides. 

Fig. 2.3.4. Proposed binding mode for complexation of carboxylates by guanidiniocarbonyl pyrrole receptors like 2.

These qualitative assays show that one-armed cationic guanidiniocarbonyl pyrrole receptors can indeed effectively bind tetrapeptides even in water. Molecular modeling studies suggest a complex structure as shown for one specific example, the receptor Val-Val-Val-CBS, in Figure 2.3.11. Receptor and substrate form a hydrogen bonded //-sheet which is further stabilized by additional hydrophobic interactions between the apolar groups in the side-chains. Recognition of the tetrapep-tide thus seems to be controlled by a fine balanced interplay between electrostatic and hydrophobic interactions. 

R 43 C. Schmuck and L. Geiger, Carboxylate Binding by Guanidiniocarbonyl Pyrroles From Self-Assembly to Peptide Receptors , p. 1485 R 44 X. Cai and C. Dass, Conformational Analysis of Proteins and Peptides , p. 1841 Vol. 8, 2004... 

Alternatively, optimization of peptide affinity and selectivity of guanidiniocarbonyl pyrrole-derived peptide receptors has been achieved by using combinatorial methods." In this context, a library of hosts of the general structure 41 (Scheme 20) was prepared on solid support, and binding affinity was screened toward the N-protected tetrapep-tide Ac-Val-Val-Ile-Ala-0 , the C-terminal sequence of the amyloid-)S-peptide. The first investigation involved a library... 

An example of a positively charged receptor that binds to phosphate esters of monosaccharides is 18 (Scheme 12). This compound contains three guanidiniocarbonyl pyrrole-derived substituents around the aromatic core, a building block introduced by the Schmuck group as a binding site for... 

Scheme 21. 5-(Guanidiniocarbonyl)pyrrole-2-carboxylate tris(pyrrolidino)phosphine oxide solvate (VAFRIE [109])...

Schlund S, Schmuck C, Engels B (2005) Knock-ouf analogues as a tool to quantify supra-molecular processes a theoretical study of molecular interactions in guanidiniocarbonyl pyrrole carboxylate dimers J Am Chem Soc 127 11115 11124... 

Schmuck and coworkers [43] recentiy reported that by attaching the self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterionic moieties to the amino groups of polyethyleneimine (PEI), the polymer can be converted to a pH switchable hydrogel. After functionalization (18, Scheme 6.6), PEI was transformed from a viscous liquid to a solid. Using the characteristic UV absorption of the GCP group, the approximate loading of the zwitterionic units onto the polymer was calculated to be 40 %. This was further confirmed by GPC analysis of the molecular mass of the functionalized polymer. The functionalized PEI polymer 18 was readily soluble in water but produced more viscous samples than that observed with PEI. 

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