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Literature Meeting
M. Ehsan
Bionano Chemistry Lab
Introduction
Supramolecular Polymer
A supramolecular polymer is a polymer whose monomer repeat units are
held together by noncovalent bonds.
Coordination
π-π interactions
 hydrogen bonding
Quadruple hydrogen bonds
Hydrogen Bond Quadruple AngewChemIntEd 1998 v37 p75
EurJOrgChem page2565 year1998
• Peptide-amphiphiles are attractive candidate biomaterials for
bio-nanotechnology and tissue engineering
• applications ranging from controlled gene and drug release,
• skin care,
• nanofabrication,
• biomineralization,
• membrane protein stabilization
• 3D cell culture and tissue engineering.
Synthetic Strategy
Fig. 1 Schematic representation of the chemical structures of pyrenei midazolium labeled peptide and viologen
functionalised PNIPAAm and the formation of a ternary complex with CB[8].
 Cucurbiturils are macrocyclic molecules made of glycoluril (=C4H2N4O2)
monomers linked by methylene bridges.
 drug delivery, asymmetric synthesis, molecular switching, and dye tuning
 Cucurbit[8]uril (CB[8]) ternary complex system offers strong binding of
two complementary motifs (binding constants Keq = 1012 M-2) in water
 The CB[8] is an attractive choice for building stable, modular
supramolecular structures in an aqueous environment via a non-covalent
route.
Acta Crystallogr B, 1984, 382-387
Cucurbituril gyroscope AngewChemInt
Ed 2002 v41 p275
Supramolecular Polymeric Peptide Vesicle Formation
Fig. 2 Schematic representation of the temperature induced formation of a supramolecular
polymeric peptide vesicle.
Thermoresponsive Behaviour
Fig. Thermoresponsive behaviour of 1 + 2 with and without CB[8]
(0.05 mM).
TEM micrographs of supramolecular vesicles at 37 oC (solution concentration = 0.05
mM).
Particle size distributions of supramolecular vesicles at 37 oC.
Critical Aggregation Concentration (CAC)
Figure : Determination of the CAC of the supramolecular vesicles in (a) deionised water and
(b) 1X phosphate buffer saline (PBS) solution containing 1% fetal bovine serum (FBS) at pH
7.4
Basic fibroblast growth factor (bFGF)
 Basic fibroblast growth factor is a mitogenic cytokine protein
 Regulates many aspects of cellular activity, such as cell migration and
extracellular matrix metabolism.
 bFGF degrades rapidly when the external environment is above 40 oC or
when the pH is less than 5,
 Heparin is required to stabilise the protein and to
preserve its bioactivity
 The efficacy of bFGF in vivo is also limited
its short lifetime and
susceptibility to enzymatic degradation
http://en.wikipedia.org/wiki/Basic_fibroblast_growth_factor
• Various approaches have been proposed for the stabilization of bFGF.
• These include the
 Chemical modification techniques,
 Encapsulation in gels and
 Powder formulation.
• Vesicles are highly attractive carriers for proteins due to their hydrophilic
interior.
• minimises the risk of protein denaturation as it does not expose
the protein to extremes in temperatures or organic solvents
Encapsulation Effect on the Immunoreactivity of bFGF
Fig. 4 (a) Assessment of immunoreactive bFGF in vesicles after encapsulation
at various times
Bioactivity of bFGF
(b) Bioactivity of bFGF following storage in vesicles
after encapsulation at various times.
Effect of freeze-thaw denaturing conditions as compared to
heparin treatment on the bioactivity of bFGF encapsulated in the
vesicles.
Release Behavior
Figure : bFGF release (37 oC) from the vesicles made from the ternary complexes.
Conclusion
• Protein-friendly nature of the vesicles was demonstrated
by encapsulating bioactive bFGF into the supramolecular
nanocarriers without the use of stabilising agents
• The supramolecular vesicles could potentially be used as
injectable carriers for the release of bioactive cytokines for
tissue repair and other related applications

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Supramolecular polymeric peptide amphiphile

  • 1. Impact Factor 6.378 Literature Meeting M. Ehsan Bionano Chemistry Lab
  • 2. Introduction Supramolecular Polymer A supramolecular polymer is a polymer whose monomer repeat units are held together by noncovalent bonds. Coordination π-π interactions  hydrogen bonding Quadruple hydrogen bonds Hydrogen Bond Quadruple AngewChemIntEd 1998 v37 p75 EurJOrgChem page2565 year1998
  • 3. • Peptide-amphiphiles are attractive candidate biomaterials for bio-nanotechnology and tissue engineering • applications ranging from controlled gene and drug release, • skin care, • nanofabrication, • biomineralization, • membrane protein stabilization • 3D cell culture and tissue engineering.
  • 4. Synthetic Strategy Fig. 1 Schematic representation of the chemical structures of pyrenei midazolium labeled peptide and viologen functionalised PNIPAAm and the formation of a ternary complex with CB[8].
  • 5.  Cucurbiturils are macrocyclic molecules made of glycoluril (=C4H2N4O2) monomers linked by methylene bridges.  drug delivery, asymmetric synthesis, molecular switching, and dye tuning  Cucurbit[8]uril (CB[8]) ternary complex system offers strong binding of two complementary motifs (binding constants Keq = 1012 M-2) in water  The CB[8] is an attractive choice for building stable, modular supramolecular structures in an aqueous environment via a non-covalent route. Acta Crystallogr B, 1984, 382-387 Cucurbituril gyroscope AngewChemInt Ed 2002 v41 p275
  • 6. Supramolecular Polymeric Peptide Vesicle Formation Fig. 2 Schematic representation of the temperature induced formation of a supramolecular polymeric peptide vesicle.
  • 7.
  • 8. Thermoresponsive Behaviour Fig. Thermoresponsive behaviour of 1 + 2 with and without CB[8] (0.05 mM).
  • 9. TEM micrographs of supramolecular vesicles at 37 oC (solution concentration = 0.05 mM). Particle size distributions of supramolecular vesicles at 37 oC.
  • 10. Critical Aggregation Concentration (CAC) Figure : Determination of the CAC of the supramolecular vesicles in (a) deionised water and (b) 1X phosphate buffer saline (PBS) solution containing 1% fetal bovine serum (FBS) at pH 7.4
  • 11. Basic fibroblast growth factor (bFGF)  Basic fibroblast growth factor is a mitogenic cytokine protein  Regulates many aspects of cellular activity, such as cell migration and extracellular matrix metabolism.  bFGF degrades rapidly when the external environment is above 40 oC or when the pH is less than 5,  Heparin is required to stabilise the protein and to preserve its bioactivity  The efficacy of bFGF in vivo is also limited its short lifetime and susceptibility to enzymatic degradation http://en.wikipedia.org/wiki/Basic_fibroblast_growth_factor
  • 12. • Various approaches have been proposed for the stabilization of bFGF. • These include the  Chemical modification techniques,  Encapsulation in gels and  Powder formulation. • Vesicles are highly attractive carriers for proteins due to their hydrophilic interior. • minimises the risk of protein denaturation as it does not expose the protein to extremes in temperatures or organic solvents
  • 13. Encapsulation Effect on the Immunoreactivity of bFGF Fig. 4 (a) Assessment of immunoreactive bFGF in vesicles after encapsulation at various times
  • 14. Bioactivity of bFGF (b) Bioactivity of bFGF following storage in vesicles after encapsulation at various times. Effect of freeze-thaw denaturing conditions as compared to heparin treatment on the bioactivity of bFGF encapsulated in the vesicles.
  • 15. Release Behavior Figure : bFGF release (37 oC) from the vesicles made from the ternary complexes.
  • 16. Conclusion • Protein-friendly nature of the vesicles was demonstrated by encapsulating bioactive bFGF into the supramolecular nanocarriers without the use of stabilising agents • The supramolecular vesicles could potentially be used as injectable carriers for the release of bioactive cytokines for tissue repair and other related applications