Hydrophobic Peptide Channels and Encapsulated Water Wires

Abstract

Peptide nanotubes with filled and empty pores and close-packed structures are formed in closely related pentapeptides. Enantiomorphic sequences, Boc-(D)Pro-Aib-Xxx-Aib-Val-OMe (Xxx = Leu, 1; Val, 2; Ala, 3; Phe, 4) and Boc-Pro-Aib-(D)Xxx-Aib-(D)Val-OMe ((D)Xxx = (D)Leu, 5; (D)Val, 6; (D)Ala, 7; (D)Phe, 8), yield molecular structures with a very similar backbone conformation but varied packing patterns in crystals. Peptides 1, 2, 5, and 6 show tubular structures with the molecules self-assembling along the crystallographic six-fold axis (c-axis) and revealing a honeycomb arrangement laterally (ab plane). Two forms of entrapped water wires have been characterized in 2: 2a with d(O...O) = 2.6 A and 2b with d(O...O) = 3.5 A. The latter is observed in 6 (6a) also. A polymorphic form of 6 (6b), grown from a solution of methanol-water, was observed to crystallize in a monoclinic system as a close-packed structure. Single-file water wire arrangements encapsulated inside hydrophobic channels formed by peptide nanotubes could be established by modeling the published structures in the cases of a cyclic peptide and a dipeptide. In all the entrapped water wires, each water molecule is involved in a hydrogen bond with a previous and succeeding water molecule. The O-H group of the water not involved in any hydrogen bond does not seem to be involved in an energetically significant interaction with the nanotube interior, a general feature of the one-dimensional water wires encapsulated in hydrophobic environments. Water wires in hydrophobic channels are contrasted with the single-file arrangements in amphipathic channels formed by aquaporins.

Modelling water molecules inside cyclic peptide nanotubes

“…Their results agree with Engels et al (1995) who also state that the water molecules prefer to be in the free space between each peptide ring. However, results of Song et al (2013), Liu et al (2010), Engels et al (1995) contradict the findings of Raghavender et al (2009Raghavender et al ( , 2010) that in tubes with diameters ranging from 5.2 to 7.7 Å , water molecules align in a single file along the long axis of a peptide nanotube.…”

“…7). By considering this, we are able to predict whether the equilibrium arrangement of the water molecules inside the peptide nanotube will be a single file as seen in Raghavender et al (2009Raghavender et al ( , 2010 or a 1 À 2 À 1 À 2 file as suggested by Engels et al (1995), Song et al (2013), Liu et al (2010). In this section, we assume that the peptide nanotube only comprises two peptide units.…”

Small Molecules and Peptides Inside Carbon Nanotubes: Impact of Nanoscale Confinement

“…Molecules confined inside nanoscale space such as narrow nanotubes or membrane proteins can form one-dimensional (1D) molecular wires, which have attracted intense interest recently because of their scientific importance and potential applications in nanotechnology [1,21,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. Among them, it is of particular interest in determining the structure and dynami-cal behavior of water wires [1,21,[40][41][42][43][44][45][46][47][48][49] which have been found to exist in narrow nanotubes [1,21,[40][41][42][46][47][48] and biological channels [43][44][45].…”

“…Among them, it is of particular interest in determining the structure and dynami-cal behavior of water wires [1,21,[40][41][42][43][44][45][46][47][48][49] which have been found to exist in narrow nanotubes [1,21,[40][41][42][46][47][48] and biological channels [43][44][45]. Water wires have many interesting properties, such as wavelike density distributions [1,46], rapid and concerted motions [1,40,43], orientation-ordered structures and collective flips [1,21,41,48], and excellent on-off gating behaviors [46,47].…”

“…13b). Meanwhile, the aromatic sidechains of Trp 43 , Tyr 45 , and Phe 52 in the beta-region were tightly stuck to the inner wall of CNT by their strong π-π stacking interactions. A helix-like structure was formed in the turn segment [ Figs The polyalanine chain was then utilized as the model system to study the stability of helix in CNT confinement.…”