Peptides and peptidomimetics that behave as low molecular weight gelators

Gelators may be divided into chemical gels and physical gels: the internal structure of chemical gels is made of chemical bonds, while physical gels are characterized by dynamic cross-links that are constantly created and broken, changing their state between solid and liquid under influence of environmental factors. The gelator present in physical gels may be an inorganic or a organic compound, the latter having a molecular weight ≤ 500 amu. These compounds are generally called “low molecular weight gelators” (LMWGs). Some general requirements are needed for the preparation of a good gelator: (i) it should not be too soluble neither too insoluble; (ii) it should contain a hydrophilic head, as a peptide bond or a urea bonds; (iii) it should contain some hydrophobic moieties, usually aromatic rings or occasionally long aliphatic chains; (iv) it should be a chiral compound. In this tutorial review we want to focus our attention on short peptides or peptidomimetics that behave as LMWGs: we will call them PLMWGs. Several peptide gelators contain a Phe moiety: some authors have shown that on replacing the Phe group with an Ala group the gelation does not occur. Peptidomimetics are small protein-like molecules designed to mimic natural peptides. To efficiently design a peptidomimetic, local constrains must be introduced in the skeleton, to induce the formation of preferred secondary structures. Thus the introduction of a constrain (a cyclobutane or a oxazolidin-2-one ring) or the preparation of C3-simmetric compounds produces efficient gelators. Excellent results were obtained also with amphiphilic or bolaamphiphilic gelators. These molecules consist of three segments: (i) a hydrophobic sequence, which is commonly an alkyl tail; (ii) a beta-sheet-forming peptide that promotes nanofibre formation; (iii) a peptide segment that contains ionizable side chains and often an amino acid sequence of interest for biological signaling.