Secondary Structure:

1
Secondary Structure b-sheet
Almost fully extended conformation
2
Secondary Structure b-sheet
3
Secondary Structure b-sheet
Sidechains protrude on alternate sides
4
Secondary Structure parallel b-sheet
5
Secondary Structure anti-parallel b-sheet
6
Secondary Structure b-sheet
parallel beta-sheet 3.2Å / aa anti-parallel
beta-sheet 3.4Å / aa alpha-helix 1.5Å / aa
In ribbon representation of proteins the arrows
of beta-strands point toward C-terminus
Anti-parallel
Parallel
7
Beta-Sheet Design
8
Self-assembling peptide nanotubes
Intertubular H-bonds
9
Relative sheet register
D
L
D
D
10
TEM image of need-like crystals of peptide
nanotubes
11
TEM image of a need-like crystal of peptide
nanotubes
12
Electron diffraction pattern collected from a
nanotube crystal
13
Top view of a nanotube dimer
14
Proposed crystal structure of peptide nanotubes
15
pH-sensitive self-assembly
16
Hydrophobic peptide nanotube
17
Peptide nanotube transmembrane channels
18
Self-Assembling Peptide Nanotubes
cyclic-peptides self-assembled into open
tubes consist of an even number of alternated
D / L amino acids formation of anti-parallel
hydrogen bonded network assembly could be
controlled by electrostatic interactions
assembly could be directed toward particular
environments (hydrophobic) by selection of amino
acids are functional material (ion channel
antibiotic)
19
Self-Assembling Peptide-Amphiphiles

• Alkyl tail to provide hydrophobicity
• Cysteines for intermolecular crosslinking
• Glycines to provide a flexible linker
• Phosphoserine for hydroxyapatite mineralization
• RGD for cell adhesion

Jeffrey D. Hartgerink, Elia Beniash, Samuel I.
Stupp, Science, November 23, 2001
20
The Charged Headgroup Gives the Molecule a pH
Switch
O
P
O
O
At pH 7 the molecule has a net charge of -3
O
O
O
O
O
O
O
O
O
O
P
O
At pH below 4 the negative charges are neutralized
O
O
O
O
O
O
O
21
pH-controlled assembly-disassembly of peptide
nanofibers
22
Negative Stain TEM reveals that the Gel is
Composed of Fibers with a Diameter of 5-8nm and
Microns Long
Jeffrey D. Hartgerink, Elia Beniash, Samuel I.
Stupp, Science, November 23, 2001
23
Model of the Self-Assembled Peptide Nanofiber
H
OH-
Jeffrey D. Hartgerink, Elia Beniash, Samuel I.
Stupp, Science, November 23, 2001
24
Covalent Capture is Possible Through the
Formation of Intermolecular Disulfide Bonds
25
Length of Aliphatic Tail Controls Self-Assembly
26
Negative Stain TEM of PA nanofibers with C10
alkyl tail