From little things big things grow: 14‐Helical N‐acetyl β3‐peptides spontaneously self‐assemble in a unique head‐to‐tail fashion to form fibers from solution. The fiber size can be controlled from the nano‐ to the macroscale. The inherent flexibility in design and ease of synthesis provide powerful new avenues for the development of novel bio‐ and nanomaterials by supramolecular self‐assembly.

No abstract

Insulin-like peptide 3 (INSL3) is a member of the insulin superfamily that plays an important role in mediating testes descent during fetal development. More recently, it has also been demonstrated to initiate oocyte maturation and suppress male germ cell apoptosis. These actions are mediated via a specific G-protein-coupled receptor, LGR8. Little is known regarding the structure and function relationship of INSL3, although it is believed that the principal receptor binding site resides within its B-chain. We subsequently observed that the linear B-chain alone (INSL3B-(1-31)) bound to LGR8 and was able to antagonise INSL3 stimulated cAMP accumulation in HEK-293T cells expressing LGR8. Sequentially N-and C-terminally shortened linear analogs were prepared by solid phase synthesis and subsequent assay showed that the minimum length required for binding was residues 11-27. It was also observed that increased binding affinity correlated with a corresponding increase in ␣-helical content as measured by circular dichroism spectroscopy. Molecular modeling studies suggested that judicious placement of a conformational constraint within this peptide would increase its ␣-helix content and result in increased structural similarity to the B-chain within native INSL3. Consequently, intramolecularly disulfide-linked analogs of the B-chain showed a potentiation of INSL3 antagonistic activity, as well as exhibiting increased proteolytic stability, as assessed in rat serum in vitro. Administration of one of these peptides into the testes of rats resulted in a substantial decrease in testis weight probably due to the inhibition of germ cell survival, suggesting that INSL3 antagonists may have potential as novel contraceptive agents. Insulin-like peptide 3 (INSL3)3 is a member of the insulin superfamily of hormones, which also includes insulin-like growth factors I and II (IGF-I and -II), relaxin-1, -2, and -3, and INSL4, -5, and -6. INSL3 is a 6-kDa peptide consisting of two chains (A and B) linked by two intermolecular disulfide bonds, with a third intermolecular disulfide bond in the A-chain (Fig. 1) (1). It is expressed primarily in the Leydig cells of fetal and adult testes and in the thecal cells of the ovary (1). The receptor for INSL3 has recently been identified and shown to belong to the family of leucine-rich repeat-containing G-protein-coupled receptors (LGRs) (2). INSL3 binds with high affinity to LGR8 and has very low affinity for the paralagous receptor LGR7, which is the receptor for relaxin (3). It is now well accepted that INSL3 is a member of the relaxin peptide family (4), and LGR7 and LGR8 have been classified as relaxin family peptide receptors, RXFP1 and RXFP2, respectively (5). Importantly, relaxin can bind to and activate LGR8 in some species, although with lesser affinity and potency than INSL3 (6,7).Although the precise physiological functions of INSL3 have not been fully determined, it has been shown to play a pivotal role in testicular descent and ovarian function. In male mice, deletion of either the ...

Peptides comprised entirely of β-amino acids, or β-peptides, have attracted substantial interest over the past 25 years due to their unique structural and chemical characteristics. β-Peptides form well-defined secondary structures that exhibit different geometries compared with their α-peptide counterparts, giving rise to their foldamer classification. β-Peptide foldamers can be functionalized easily and are metabolically stable and, together with the predictable side-chain topography, have led to the design of a growing number of bioactive β-peptides with a range of biological targets. The strategic engineering of chemical and topographic properties has also led to the design of β-peptide mimics of higher-order oligomers. More recently, the ability of these peptides to self-assemble into complex structures of controlled geometries has been exploited in materials applications. The focus of this mini-review is on how the unique structural features of β-peptide assemblies have been exploited in the design of self-assembled proteomimetic bundles and nanomaterials.