Tal-Gan Research Group

2024

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Guo, M., Renshaw, C. P., Mull, R. W., Tal-Gan, Y. Noncanonical Streptococcus sanguinis ComCDE circuitry integrates environmental cues in transformation outcome decision. Cell Chem. Biol., 2024, 31, 298-311.e6.

https://doi.org/10.1016/j.chembiol.2023.09.007

 

2023

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Milly, T. A., Renshaw, C. P., Tal-Gan, Y. Developing Multi-Species Quorum Sensing Modulators Based on the Streptococcus mitis Competence-Stimulating Peptide. J. Biol. Chem., 2023, 299, 105448.

https://doi.org/10.1016/j.jbc.2023.105448

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Proutière, A., Merle D. L., Garcia-Lopez, M., Léger, C., Voegele, A., Chenal, A., Harrington, A., Tal-Gan, Y., Cokelaer, T., Trieu-Cuot, P., Dramsi, S. Gallocin A, an Atypical Two-Peptide Bacteriocin with Intramolecular Disulfide Bonds Required for Activity. Microbiol. Spectr., 2023, 11, e05085-22.

https://doi.org/10.1128/spectrum.05085-22

 

McBrayer, D. N., Ghosh, U., Lella, M., Cameron, C. D., Tal-Gan, Y. Peptoid-Peptide Hybrid Analogs of the Enterococcus faecalis Fsr Auto-Inducing Peptide (AIP) Reveal Crucial Structure-Activity Relationships. ChemBioChem, 2023, 24, e202200527.

https://doi.org/10.1002/cbic.202200527

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Milly, T. A., Tal-Gan, Y. Targeting Peptide-Based Quorum Sensing Systems for the Treatment of Gram-Positive Bacterial Infections. Pept. Sci., 2023, 115, e24298.

https://doi.org/10.1002/pep2.24298

 

2022

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Brennan​, A. A., Harrington, A., Guo, M., Renshaw, C. P., Tillett​, R. L., Miura, P., Tal-Gan, Y. Investigating the Streptococcus sinensis competence regulon through a combination of transcriptome analysis and phenotypic evaluation. Microbiology, 2022, 168, 001256

https://doi.org/10.1099/mic.0.001256

 

Brennan, A. A., Mehrani, M., Tal-Gan, Y. Modulating Streptococcal Phenotypes using Signal Peptide Analogs. Open Biol., 2022, 12, 220143.

https://doi.org/10.1098/rsob.220143

 

Oh, W.H., Lella, M.,  Kuo, S. H., Tal-Gan, Y., Lau, G.W.  Pharmacological Evaluation of Synthetic Dominant-Negative Peptides Derived from the Competence Stimulating Peptide of Streptococcus pneumonia. ACS Pharmacol. Transl. Sci., 2022, 5, 299-305.

https://doi.org/10.1021/acsptsci.2c00037

​

This article was highlighted by

• Pharmacology & Translational Science virtual special issue

“New Drug Modalities in Medicinal Chemistry, Pharmacology, and Translational Science.”

​

Lella, M., Oh, W.H., Kuo, S. H., Lau, G.W., Tal-Gan, Y. Attenuating the Streptococcus pneumoniae Competence Regulon using Urea-Bridged Cyclic Dominant Negative CSP Analogs. J. Med. Chem., 2022, 65, 6826-6839.

https://doi.org/10.1021/acs.jmedchem.2c00148

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Milly, T.A., Buttner, A. R., Rieth, N., Hutnick, E., Engler, E. R., Campanella, A. R., Lella, M., Bertucci, M. A., Tal-Gan, Y. Optimizing CSP1 Analogs for Modulating Quorum Sensing in Streptococcus pneumoniae with Bulky, Hydrophobic Nonproteogenic Amino Acid Substitutions. RSC Chem. Biol., 2022, 3, 301-311.

https://doi.org/10.1039/D1CB00224D

 

Reid, K.M., Singh, A.K., Bikash, C.R., Wei. J., Tal-Gan, Y., Vinh, Q.N., Leitner, D.M. The origin and impact of bound water around intrinsically disordered proteins. Biophys. J, 2022, 121, 540-551.

https://doi.org/10.1016/j.bpj.2022.01.011

​

2021

​

Mull, R.W., Tal-Gan, Y. Elucidating the Role and Structure-Activity Relationships of the Streptococcus oligofermentans Competence Stimulating Peptide. ACS Chemical Biology, 2021,  16, 2834–2844.

https://pubs.acs.org/doi/full/10.1021/acschembio.1c00746

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Milly, T. A., Engler, E. R., Chichura, K. S., Buttner, A. R., Koirala, B., Tal-Gan, Y., Bertucci, M. A. Harnessing multiple, non-proteogenic substitutions to optimize CSP:ComD hydrophobic interactions in group1 Streptococcus pneumoniae. ChemBioChem, 2021,  22, 1940-1947.

https://doi.org/10.1002/cbic.202000876

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Lella, M., Tal-Gan, Y. Strategies to Attenuate the Competence Regulon in Streptococcus pneumoniae. Pept. Sci, 2021, e24222

https://doi.org/10.1002/pep2.24222

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Harrington, A., Proutière, A., Mull, R. W., du Merle, L., Dramsi, S., Tal-Gan, Y. Secretion, Maturation and Activity of a Quorum Sensing Peptide (GSP) Inducing Bacteriocins Transcription in Streptococcus gallolyticus. mBio., 2021, 12, e03189-20.

https://doi.org/10.1128/mBio.03189-20

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2020

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Bikash, C. R., Tal-Gan, Y. Structure Activity Relationship Study of the XIP Quorum Sensing Pheromone in Streptococcus mutans Reveal Inhibitors of the Competence Regulon. ACS Chem. Biol., 2020,  15, 2833–2841.

https://doi.org/10.1021/acschembio.0c00650

 

Mull, R. W., Brennan, A. A., Russ, B. R., Tal-Gan, Y. Attenuating the Selection of Vancomycin Resistance Among Enterococci Through the Development of Peptide-Based Vancomycin Antagonists. ACS Infect. Dis., 2020, 6, 2913-2925.

https://doi.org/10.1021/acsinfecdis.0c00319

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McBrayer, D. N., Cameron, C. D., Tal-Gan, Y. Development and utilization of peptide-based quorum sensing modulators in Gram-positive bacteria. Org. Biomol. Chem. 2020, 18, 7273-7290.

https://doi.org/10.1039/D0OB01421D

 

Milly, T. A., Tal-Gan, Y. Biological Evaluation of Native Streptococcal Competence Stimulating Peptides Reveal Potential Crosstalk Between Streptococcus mitis and Streptococcus pneumoniae and a New Scaffold for the Development of S. pneumoniae Quorum Sensing Modulators. RSC Chem. Biol., 2020, 1, 60-67 (Cover).

https://doi.org/10.1039/D0CB00012D

• This article was selected to the RSC Chemical Biology ‘Analytical Methods in Chemical Biology’ Collection (2021):

https://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=cb&themeid=20322a6c-6e73-42d5-b94e-3679038adcfb

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Yang, Y., Lin, J., Harrington, A., Cornilescu, G., Lau, G. W., Tal-Gan, Y. Designing Cyclic Competence Stimulating Peptide (CSP) Analogs with Pan-group Quorum-Sensing Inhibition Activity in Streptococcus pneumoniae. Proc. Natl. Acad. Sci. USA, 2020, 117, 1689-1699.

https://doi.org/10.1073/pnas.1915812117

​

This article was highlighted by:

• PNAS “In this Issue”:

https://www.pnas.org/content/117/3/1237

• UNR Nevada Today:

​https://www.unr.edu/nevada-today/news/2020/peptides-research-breakthrough

• Nevada Public Radio:

https://knpr.org/knpr/2020-02/unr-researchers-aim-stop-spread-bacteria-disrupting-communication

• KOLO 8 News Now:

https://www.kolotv.com/content/news/UNR-Researchers--568158461.html

​

Koirala, B., Tal-Gan, Y. Development of Streptococcus pneumoniae Pan Group Quorum Sensing Modulators. ChemBioChem. 2020, 21, 340-345 (Cover).

https://doi.org/10.1002/cbic.201900365

 

2019

 

Harrington, A., Tal-Gan, Y. The Importance of Amide Protons in Peptide Drug Development. Future Med. Chem. 2019, 11, 2759-2763. 

https://doi.org/10.4155/fmc-2019-0238

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Yang, Y., Tal-Gan, Y. Exploring the Competence Stimulating Peptide (CSP) N-terminal Requirements for Effective ComD Receptor Activation in Group1 Streptococcus pneumoniae. Bioorg. Chem. 2019, 89, 102987.

https://doi.org/10.1016/j.bioorg.2019.102987

​

Koirala, B., Phillips, N. R., Tal-Gan, Y. Unveiling the Importance of Amide Protons in CSP:ComD Interactions in Streptococcus pneumoniae. ACS Med. Chem. Lett. 2019, 10, 880-886.

https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00038

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McBrayer, D. N., Tal-Gan, Y. Deciphering bacterial signalling. Nat. Chem. 2019, 11, 398-399.

https://www.nature.com/articles/s41557-019-0265-2

​

McBrayer, D. N., Gantman, B. K., Tal-Gan, Y. N-methylation of Amino Acids in Gelatinase Biosynthesis-Activating Pheromone (GBAP) Identifies Key Site for Stability Enhancement with Retention of the Enterococcus faecalis Fsr Quorum Sensing Circuit Response. ACS Infect. Dis. 2019, 5, 1035-1041.

https://pubs.acs.org/doi/10.1021/acsinfecdis.9b00097

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Bikash, C. R., Tal-Gan, Y. Identification of Highly Potent Competence Stimulating Peptide-Based Quorum Sensing Activators in Streptococcus mutans Through the Utilization of N-Methyl and Reverse Alanine Scanning. Bioorg. Med. Chem. Lett., 2019, 29, 811-814.
https://www.sciencedirect.com/science/article/pii/S0960894X19300320

 

2018

 

Koirala, B., Lin, J., Lau, G. W., Tal-Gan, Y. Development of a Dominant Negative Competence Stimulating Peptide (dnCSP) that Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute Pneumonia. ChemBioChem, 2018, 19, 2380-2386 (VIP Paper). 

https://onlinelibrary.wiley.com/doi/10.1002/cbic.201800505

 

McBrayer, D. N., Cameron, C. D., Gantman, B. K., Tal-Gan, Y. Rational Design of Potent Activators and Inhibitors of the Enterococcus faecalis Fsr Quorum Sensing Circuit. ACS Chem. Biol., 2018, 13, 2673-2681.

https://pubs.acs.org/doi/10.1021/acschembio.8b00610

​

Yang, Y., Cornilescu, G., Tal-Gan, Y. Structural Characterization of Competence Stimulating Peptide Analogues Reveals Key Features for ComD1 and ComD2 Receptor Binding in Streptococcus pneumoniae. Biochemistry, 2018, 57, 5359-5369. 

https://pubs.acs.org/doi/10.1021/acs.biochem.8b00653

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​Koirala, B., Hillman, R. A., Tiwold, E. K., Bertucci, M. A., Tal-Gan, Y. Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae. Beilstein J. Org. Chem., 2018, 14, 1769-1777. 

https://www.beilstein-journals.org/bjoc/articles/14/151

​

Bikash, C. R., Hamry, S. R., Tal-Gan, Y. Structure−Activity Relationships (SARs) of the Competence Stimulating Peptide (CSP) in Streptococcus mutans Reveal Motifs Critical for Membrane Protease SepM Recognition and ComD Receptor Activation. ACS Infect. Dis., 2018, 4, 1385-1394.

10.1021/acsinfecdis.8b00115

​

Mull, R. W., Harrington, A., Sanchez, L. A., Tal-Gan, Y. Cyclic Peptides That Govern Signal Transduction Pathways: From Prokaryotes to Multi-Cellular Organisms. Curr. Top. Med. Chem., 2018, 18, 625-644.

10.2174/1568026618666180518090705

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Rubin, S. J. S., Tal-Gan, Y., Gilon, C., Qvit, N. Conversion of Protein Active Regions into Peptidomimetic Therapeutic Leads using Backbone Cyclization and Cycloscan – Do It Yourself. Curr. Top. Med. Chem., 2018, 18, 556-565.

10.2174/1568026618666180518094322

​

Harrington, A., Tal-Gan, Y. Identification of Streptococcus gallolyticus subsp. gallolyticus (biotype I) competence stimulating peptide pheromone. J. Bacteriol., 2018, 200, e00709-17 (Cover).

https://jb.asm.org/content/200/14/e00709-17

 

2017

 

McBrayer, D. N., Tal-Gan, Y. Recent Advances in GLP-1 Receptor Agonists for Use in Diabetes Mellitus. Drug Dev. Res., 2017, 78, 292-299.

http://onlinelibrary.wiley.com/doi/10.1002/ddr.21404/abstract

​

McBrayer, D. N., Gantman, B. K., Cameron, C. D., Tal-Gan, Y. An Entirely Solid Phase Peptide Synthesis-Based Strategy for Synthesis of Gelatinase Biosynthesis-Activating Pheromone (GBAP) Analogue Libraries: Investigating the Structure-Activity Relationships of the Enterococcus faecalis Quorum Sensing Signal. Org. Lett., 2017, 19, 3295-3298.
http://pubs.acs.org/doi/abs/10.1021/acs.orglett.7b01444

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Yang, Y., Koirala, B., Sanchez, L. A., Phillips, N. R., Hamry, S. R., Tal-Gan, Y. Structure-Activity Relationships of the Competence Stimulating Peptides (CSPs) in Streptococcus pneumoniae Reveal Motifs Critical for intra-group and cross-group ComD Receptor Activation. ACS Chem. Biol., 2017, 12, 1141-1151.
http://pubs.acs.org/doi/abs/10.1021/acschembio.7b00007

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Vasquez, J. K., Tal-Gan, Y., Cornilescu, G., Tyler, K. A., Blackwell, H. E. Simplified AIP-II Peptidomimetics are Potent Inhibitors of Staphylococcus aureus AgrC Quorum Sensing Receptors. ChemBioChem, 2017, 18, 413-423
http://onlinelibrary.wiley.com/wol1/doi/10.1002/cbic.201600516/full

 

2016

 

Tal-Gan, Y., Ivancic, M., Cornilescu, G., Yang, T., Blackwell, H.E. Highly Stable, Amide-Bridged Autoinducing Peptide Analogs that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus. Angew. Chem. Int. Ed., 2016, 55, 8913-8917.
http://onlinelibrary.wiley.com/doi/10.1002/anie.201602974/full

​

Yang, T., Tal-Gan, Y., Paharik, A.E., Horswill, A.R., Blackwell, H.E. Structure-Function Analyses of the Autoinducing Peptide I from Staphylococcus epidermidis Reveals Motifs Critical For Potent Group-Specific, Pan-Group, and Species-Specific Modulation of AgrC Quorum Sensing Receptors and Biofilm Formation. ACS Chem. Biol., 2016, 11, 1982-1991.
http://pubs.acs.org/doi/abs/10.1021/acschembio.6b00120

​

Tal-Gan, Y., Ivancic, M., Cornilescu, G., Blackwell, H.E. Characterization of Structural Elements in Native Autoinducing Peptides and Non-Native Analogues that Permit the Differential Modulation of AgrC-type Quorum Sensing Receptors in Staphylococcus aureus. Org. Biomol. Chem., 2016, 14, 113-121.
http://pubs.rsc.org/en/Content/ArticleLanding/2016/OB/C5OB01735A/Abstract

 

2015

​

Kratochvil, M.J., Tal-Gan, Y., Yang, T., Blackwell, H.E., Lynn, D.M. Nanoporous Superhydrophobic Coatings that Promote the Extended Release of Water-Labile Quorum Sensing Inhibitors and Enable Long-Term Modulation of Quorum Sensing in Staphylococcus aureus. ACS Biomater. Sci. Eng., 2015, 1, 1039-1049.
http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.5b00313

​

This article was highlighted by:

• ACS Editors’ Choice (Sept. 22, 2015)

• C&EN News:

http://cen.acs.org/articles/93/web/2015/09/Polymer-Coating-Interrupts-Bacterial-Conversations.html

 

2014

 

Tal-Gan, Y., Stacy, D.M., Blackwell, H.E. N-Methyl and Peptoid Scans of an Autoinducing Peptide Reveal New Structural Features Required for Inhibition and Activation of AgrC Quorum Sensing Receptors in Staphylococcus aureus. Chem. Commun., 2014, 50, 3000-3003.
http://pubs.rsc.org/en/content/articlelanding/2014/cc/c4cc00117f/divAbstract/

​

Broderick, A.H., Stacy, D.M., Tal-Gan, Y., Kratochvil, M.J., Blackwell, H.E., Lynn, D.M. Surface Coatings that Promote Rapid Release of Peptide-Based AgrC Inhibitors for Attenuation of Quorum Sensing in Staphylococcus aureus. Adv. Healthcare Mater., 2014, 3, 97-105.
http://onlinelibrary.wiley.com/doi/10.1002/adhm.201300119/abstract

 

2013

 

Tal-Gan, Y., Ivancic, M., Cornilescu, G., Cornilescu, C.C., Blackwell, H.E. Structural Characterization of Native Autoinducing Peptides and Abiotic Analogs Reveals Key Features Essential for Activation and Inhibition of an AgrC Quorum Sensing Receptor in Staphylococcus aureus. J. Am. Chem. Soc., 2013, 135, 18436-18444.
http://pubs.acs.org/doi/abs/10.1021/ja407533e

​

Tal-Gan, Y., Stacy, D.M., Foegen, M.K., Koenig, D.W., Blackwell, H.E. Highly Potent Inhibitors of Quorum Sensing in Staphylococcus aureus Revealed through a Systematic Synthetic Study of the Group-III Autoinducing Peptide. J. Am. Chem. Soc., 2013, 135, 7869-7882.
http://pubs.acs.org/doi/abs/10.1021/ja3112115 

​

This article was highlighted by: 

• C&EN News:

http://cen.acs.org/articles/91/web/2013/05/Silencing-Bacterial-Communications.html

• SciBX, a Nature translational science publication:

http://www.nature.com/scibx/journal/v6/n21/full/scibx.2013.520.html

• The American Society for Biochemistry and Molecular Biology (ASBMB):

http://wildtypes.wordpress.com/2013/05/13/peptide-mimics-inhibit-pathogenic-bacteria-involved-in-toxic-shock-syndrome/

• UW-Madison News:

http://www.news.wisc.edu/21812

​

Hurevich, M., Ratner-Hurevich, M., Tal-Gan, Y., Shalev, D.E., Ben-Sasson, S.Z., Gilon, C. Backbone Cyclic Helix Mimetic of Chemokine (C-C Motif) Receptor 2: A Rational Approach for Inhibiting Dimerization of G Protein-Coupled Receptors. Bioorg. Med. Chem., 2013, 21, 3958-3966.
http://www.sciencedirect.com/science/article/pii/S0968089613002320

​

Levi, I., Eskira, Y., Eisenstein, M., Gilon, C., Hoffman, A., Tal-Gan, Y., Fanous, J., Bersudsky, Y., Belmaker, R., Agam, G., Almog, O. Inhibition of inositol monophosphatase (IMPase) at the calbindin-D28k binding site: Molecular and behavioral aspects. Eur. Neuropsychopharm., 2013, 23, 1806-1815.
http://www.sciencedirect.com/science/article/pii/S0924977X15002904

 

2012

​

Horwitz, E., Tal-Gan, Y., Temper, V., Shapiro, M., Gilon, C., Hoffman, A. Chemical trapping of vancomycin - a potential strategy for preventing selection of vancomycin-resistant Enterococci. Microb. Drug Resist., 2012, 18, 109-115.
http://online.liebertpub.com/doi/abs/10.1089/mdr.2011.0057

​

Tal-Gan, Y., Naveh, S., Klein, S., Moshel, O., Levitzki, A., Gilon, C. Studying Protein-Peptide Interactions Using Benzophenone Units: A Case Study of PKB/Akt and its Inhibitor PTR6154. Anal. Biochem., 2012, 421, 750-754.
http://www.sciencedirect.com/science/article/pii/S0003269711007640

​

Naveh, S., Tal-Gan, Y., Ling, S., Hoffman, A., Holoshitz, J., Gilon, C. Developing Potent Backbone Cyclic Peptides Bearing the Shared Epitope Sequence as Rheumatoid Arthritis Drug-Leads. Bioorg. Med. Chem. Lett., 2012, 22, 493-496.
http://www.sciencedirect.com/science/article/pii/S0960894X11015058

 

2011

 

Tal-Gan, Y., Freeman, N.S., Klein, S., Levitzki, A., Gilon, C. Metabolic Stability of Peptidomimetics: N-Methyl and Aza Heptapeptide Analogs of a PKB/Akt Inhibitor. Chem. Biol. Drug Des., 2011, 78, 887-892.
http://onlinelibrary.wiley.com/doi/10.1111/j.1747-0285.2011.01207.x/abstract

​

Tal-Gan, Y., Hurevich, M., Klein, S., Ben-Shimon, A., Rosenthal, D., Hazan, C., Shalev, D.E., Niv, M.Y., Levitzki, A., Gilon, C. Backbone-Cyclic Peptide Inhibitors of Protein Kinase B (PKB/Akt). J. Med. Chem., 2011, 54, 5154-5164.
http://pubs.acs.org/doi/abs/10.1021/jm2003969

​

Freeman,N.S., Tal-Gan, Y., Klein, S., Levitzki, A., Gilon, C. Microwave-Assisted Solid-Phase Aza-peptide Synthesis: Aza Scan of a PKB/Akt Inhibitor Using Aza-arginine and Aza-proline Precursors. J. Org. Chem., 2011, 76, 3078-3085.
http://pubs.acs.org/doi/abs/10.1021/jo102422x

• This article was selected to the ACS Virtual Special Issue on Peptide Chemistry (2012):

http://pubs.acs.org/page/vi/2012/peptide.html

​

2010

 

Tal-Gan, Y., Freeman, N.S., Klein, S., Levitzki, A., Gilon, C. Synthesis and structure-activity relationship studies of peptidomimetic PKB/Akt inhibitors: The significance of backbone interactions. Bioorg. Med. Chem., 2010, 18, 2976-2985.
http://www.sciencedirect.com/science/article/pii/S0968089610001525

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Hurevich, M., Tal-Gan, Y., Klein, S., Barda, Y., Levitzki, A., Gilon, C. Novel method for the synthesis of urea backbone cyclic peptides using new Alloc protected glycine building units. J. Pept. Sci., 2010, 16, 178-185.
http://onlinelibrary.wiley.com/doi/10.1002/psc.1218/abstract