Incorporation of β-Amino Acids Enhances the Antifungal Activity and Selectivity of the Helical Antimicrobial Peptide Aurein 1.2

ACS Chemical Biology
Myung-Ryul LeeSean P Palecek

Abstract

Antimicrobial peptides (AMPs) are attractive antifungal drug candidates because they kill microbes via membrane disruption and are thus unlikely to provoke development of resistance. Low selectivity for fungal vs human cells and instability in physiological environments have limited the development of AMPs as therapeutics, but peptidomimetic AMPs can overcome these obstacles and also provide useful insight into AMP structure-function relationships. Here, we describe antifungal peptidomimetic α/β-peptides templated on the natural α-peptidic AMP aurein 1.2. These α/β-aurein analogs fold into i → i + 4 H-bonded helices that present arrays of side chain functionality in a manner virtually identical to that of aurein 1.2. By varying charge, hydrophobicity, conformational stability, and α/β-amino acid organization, we designed active and selective α/β-peptide aurein analogs that exhibit minimum inhibitory concentrations (MIC) against the opportunistic pathogen Candida albicans that are 4-fold lower than that of aurein 1.2 and elicit less than 5% hemolysis at the MIC. These α/β-aurein analogs are promising candidates for development as antifungal therapeutics and as tools to elucidate mechanisms of AMP activity and specificity.

References

Apr 15, 2000·Nature·E A PorterS H Gellman
Oct 30, 2001·FEMS Microbiology Letters·L E Cowen
Mar 5, 2003·Pharmacological Reviews·Michael R Yeaman, Nannette Y Yount
Aug 28, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Peter G PappasUNKNOWN NIAID Mycoses Study Group
Apr 18, 2007·Nature Chemical Biology·Catherine M GoodmanWilliam F DeGrado
Jul 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·W Seth HorneSamuel H Gellman
Jul 2, 2008·Accounts of Chemical Research·W Seth Horne, Samuel H Gellman
Dec 19, 2008·Chemical Biology & Drug Design·Ziqing JiangRobert S Hodges
Jan 27, 2011·Chemical Biology & Drug Design·Troels GodballeHåvard Jenssen
Aug 2, 2011·Mayo Clinic Proceedings·Russell E Lewis
Feb 9, 2012·Pakistan Journal of Biological Sciences : PJBS·Safieh Soufian, Leila Hassani
Jun 1, 2013·Organic & Biomolecular Chemistry·Youhong NiuJianfeng Cai
Mar 19, 2014·The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien Des Maladies Infectieuses Et De La Microbiologie Médicale·Shariq HaiderNkechi Azie
May 20, 2014·ACS Chemical Biology·Myung-Ryul LeeSean P Palecek

❮ Previous
Next ❯

Citations

Feb 6, 2019·Chemical Communications : Chem Comm·Imane NekkaaIstván M Mándity
Jun 19, 2019·Antimicrobial Agents and Chemotherapy·Angélica de L Rodríguez LópezSean P Palecek
Apr 4, 2020·Chemical Communications : Chem Comm·Naoto SugisawaShinichiro Fuse
Feb 11, 2021·ChemMedChem·Hidetomo YokooYosuke Demizu
Sep 18, 2018·Journal of the American Chemical Society·Takayuki Katoh, Hiroaki Suga

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.