In some naturally occurring protein sequences, an abrupt, concerted refolding from β-sheet to helical conformation occurs when the polarity of the surrounding medium drops below a critical level. This switch-like behaviour was first observed on the HIV-1 envelope glycoprotein gp120, where it plays a crucial role in the efficient binding of gp120 to the T-cell receptor CD4. Previous work had shown that an N-terminal amino acid tetrad LPCR and a Trp located 5–20 residues downstream to the tetrad are common motifs in polarity-driven switch peptides. The LPCR tetrad governs the folding of the subsequent residues and acts as a helix initiation site, whereas the Trp is responsible for the cooperative character of the structural change due to multiple, simultaneous interactions of its quadrupole moment with several amino acid residues within the sequences. Here we identify and characterize new families of switch peptides that use different, turn-probable tetrads (LPST and VPSR) as helix initiation sites at the N-terminus. We have also been able to demonstrate that some tetrads with extremely high turn probability do not serve as helix initiation sites. Comparison of these with LPCR and the newly discovered tetrads LPST and VPSR has allowed a more comprehensive description of the physico-chemical properties of helix-inducing tetrads. The deeper understanding of the intrinsic properties of switch sequences allows the design of artificial polarity-driven switches, applicable in engineering of, e.g. controllable binding sites in artificial proteins. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.