Expanding the Functional Scope of the Fmoc-Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

Vasantha Basavalingappa; Tom Guterman; Yiming Tang; Sivan Nir; Jiangtao Lei; Priyadarshi Chakraborty; Lee Schnaider; Meital Reches; Guanghong Wei; Ehud Gazit

doi:10.1002/advs.201900218

Expanding the Functional Scope of the Fmoc-Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

Vasantha Basavalingappa, Tom Guterman, Yiming Tang, Sivan Nir, Jiangtao Lei, Priyadarshi Chakraborty, Lee Schnaider, Meital Reches, Guanghong Wei^*, Ehud Gazit

^*Corresponding author for this work

Institute of Chemistry

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Peptidomimetic low-molecular-weight hydrogelators, a class of peptide-like molecules with various backbone amide modifications, typically give rise to hydrogels of diverse properties and increased stability compared to peptide hydrogelators. Here, a new peptidomimetic low-molecular-weight hydrogelator is designed based on the well-studied N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide by replacing the amide bond with a frequently employed amide bond surrogate, the urea moiety, aiming to increase hydrogen bonding capabilities. This designed ureidopeptide, termed FmocPheNHCONHPheOH (Fmoc-FuF), forms hydrogels with improved mechanical properties, as compared to those formed by the unmodified Fmoc-FF. A combination of experimental and computational structural methods shows that hydrogen bonding and aromatic interactions facilitate Fmoc-FuF gel formation. The Fmoc-FuF hydrogel possesses properties favorable for biomedical applications, including shear thinning, self-healing, and in vitro cellular biocompatibility. Additionally, the Fmoc-FuF, but not Fmoc-FF, hydrogel presents a range of functionalities useful for other applications, including antifouling, slow release of urea encapsulated in the gel at a high concentration, selective mechanical response to fluoride anions, and reduction of metal ions into catalytic nanoparticles. This study demonstrates how a simple backbone modification can enhance the mechanical properties and functional scope of a peptide hydrogel.

Original language	American English
Article number	1900218
Journal	Advanced Science
Volume	6
Issue number	12
DOIs	https://doi.org/10.1002/advs.201900218
State	Published - 19 Jun 2019

Bibliographical note

Funding Information:
V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union’s Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript.

Funding Information:
V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union's Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript.

Publisher Copyright:
© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

anion sensing
antifouling materials
metal nanoparticles
peptide self-assembly
peptidomimetics
urea slow release
ureidopeptides

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10.1002/advs.201900218

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title = "Expanding the Functional Scope of the Fmoc-Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification",

abstract = "Peptidomimetic low-molecular-weight hydrogelators, a class of peptide-like molecules with various backbone amide modifications, typically give rise to hydrogels of diverse properties and increased stability compared to peptide hydrogelators. Here, a new peptidomimetic low-molecular-weight hydrogelator is designed based on the well-studied N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide by replacing the amide bond with a frequently employed amide bond surrogate, the urea moiety, aiming to increase hydrogen bonding capabilities. This designed ureidopeptide, termed FmocPheNHCONHPheOH (Fmoc-FuF), forms hydrogels with improved mechanical properties, as compared to those formed by the unmodified Fmoc-FF. A combination of experimental and computational structural methods shows that hydrogen bonding and aromatic interactions facilitate Fmoc-FuF gel formation. The Fmoc-FuF hydrogel possesses properties favorable for biomedical applications, including shear thinning, self-healing, and in vitro cellular biocompatibility. Additionally, the Fmoc-FuF, but not Fmoc-FF, hydrogel presents a range of functionalities useful for other applications, including antifouling, slow release of urea encapsulated in the gel at a high concentration, selective mechanical response to fluoride anions, and reduction of metal ions into catalytic nanoparticles. This study demonstrates how a simple backbone modification can enhance the mechanical properties and functional scope of a peptide hydrogel.",

keywords = "anion sensing, antifouling materials, metal nanoparticles, peptide self-assembly, peptidomimetics, urea slow release, ureidopeptides",

author = "Vasantha Basavalingappa and Tom Guterman and Yiming Tang and Sivan Nir and Jiangtao Lei and Priyadarshi Chakraborty and Lee Schnaider and Meital Reches and Guanghong Wei and Ehud Gazit",

note = "Funding Information: V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union{\textquoteright}s Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript. Funding Information: V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union's Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript. Publisher Copyright: {\textcopyright} 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2019",

month = jun,

day = "19",

doi = "10.1002/advs.201900218",

language = "American English",

volume = "6",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "Wiley-VCH Verlag",

number = "12",

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TY - JOUR

T1 - Expanding the Functional Scope of the Fmoc-Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

AU - Basavalingappa, Vasantha

AU - Guterman, Tom

AU - Tang, Yiming

AU - Nir, Sivan

AU - Lei, Jiangtao

AU - Chakraborty, Priyadarshi

AU - Schnaider, Lee

AU - Reches, Meital

AU - Wei, Guanghong

AU - Gazit, Ehud

N1 - Funding Information: V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union’s Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript. Funding Information: V.B. and T.G. contributed equally to this work. This work was supported in part by grants from the European Research Council under the European Union's Horizon 2020 research and innovation program (BISON, Advanced ERC grant agreement ID: 694426) (E.G.). V.B. gratefully acknowledges the Planning and Budget Committee, Israel, for financial support. T.G. acknowledges support from the Argentinian Friends of Tel Aviv University. G.W. acknowledges the financial support from National Key Research and Development Program of China (2016YFA0501702) and the National Science Foundation of China (Grant No. 11674065). The authors thank Dr. Sigal Rencus-Lazar for language editing assistance, Dr. George Levi for HRTEM, and Omri Heifler for AFM. V.B. designed and performed the experiments. T.G. assisted in performing the catalysis and urea release experiments. Y.T., J.L., and G.W. performed the MD simulations. S.N. and M.R. performed the antifouling experiment. P.C. assisted in rheology and biocompatibilty experiments. L.S. performed the antibacterial activity experiments. V.B., T.G., and E.G. wrote the paper. All authors discussed the results and commented on the manuscript. Publisher Copyright: © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/6/19

Y1 - 2019/6/19

N2 - Peptidomimetic low-molecular-weight hydrogelators, a class of peptide-like molecules with various backbone amide modifications, typically give rise to hydrogels of diverse properties and increased stability compared to peptide hydrogelators. Here, a new peptidomimetic low-molecular-weight hydrogelator is designed based on the well-studied N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide by replacing the amide bond with a frequently employed amide bond surrogate, the urea moiety, aiming to increase hydrogen bonding capabilities. This designed ureidopeptide, termed FmocPheNHCONHPheOH (Fmoc-FuF), forms hydrogels with improved mechanical properties, as compared to those formed by the unmodified Fmoc-FF. A combination of experimental and computational structural methods shows that hydrogen bonding and aromatic interactions facilitate Fmoc-FuF gel formation. The Fmoc-FuF hydrogel possesses properties favorable for biomedical applications, including shear thinning, self-healing, and in vitro cellular biocompatibility. Additionally, the Fmoc-FuF, but not Fmoc-FF, hydrogel presents a range of functionalities useful for other applications, including antifouling, slow release of urea encapsulated in the gel at a high concentration, selective mechanical response to fluoride anions, and reduction of metal ions into catalytic nanoparticles. This study demonstrates how a simple backbone modification can enhance the mechanical properties and functional scope of a peptide hydrogel.

AB - Peptidomimetic low-molecular-weight hydrogelators, a class of peptide-like molecules with various backbone amide modifications, typically give rise to hydrogels of diverse properties and increased stability compared to peptide hydrogelators. Here, a new peptidomimetic low-molecular-weight hydrogelator is designed based on the well-studied N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide by replacing the amide bond with a frequently employed amide bond surrogate, the urea moiety, aiming to increase hydrogen bonding capabilities. This designed ureidopeptide, termed FmocPheNHCONHPheOH (Fmoc-FuF), forms hydrogels with improved mechanical properties, as compared to those formed by the unmodified Fmoc-FF. A combination of experimental and computational structural methods shows that hydrogen bonding and aromatic interactions facilitate Fmoc-FuF gel formation. The Fmoc-FuF hydrogel possesses properties favorable for biomedical applications, including shear thinning, self-healing, and in vitro cellular biocompatibility. Additionally, the Fmoc-FuF, but not Fmoc-FF, hydrogel presents a range of functionalities useful for other applications, including antifouling, slow release of urea encapsulated in the gel at a high concentration, selective mechanical response to fluoride anions, and reduction of metal ions into catalytic nanoparticles. This study demonstrates how a simple backbone modification can enhance the mechanical properties and functional scope of a peptide hydrogel.

KW - anion sensing

KW - antifouling materials

KW - metal nanoparticles

KW - peptide self-assembly

KW - peptidomimetics

KW - urea slow release

KW - ureidopeptides

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U2 - 10.1002/advs.201900218

DO - 10.1002/advs.201900218

M3 - Article

AN - SCOPUS:85064656632

SN - 2198-3844

VL - 6

JO - Advanced Science

JF - Advanced Science

IS - 12

M1 - 1900218

ER -

Expanding the Functional Scope of the Fmoc-Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

Abstract

Bibliographical note

Keywords

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