PMID- 34699170
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20221028
IS  - 1554-8937 (Electronic)
IS  - 1554-8929 (Print)
IS  - 1554-8929 (Linking)
VI  - 16
IP  - 11
DP  - 2021 Nov 19
TI  - Synthetic Natural Product Inspired Cyclic Peptides.
PG  - 2604-2611
LID - 10.1021/acschembio.1c00641 [doi]
AB  - Natural products are a bountiful source of bioactive molecules. Unfortunately, 
      discovery of novel bioactive natural products is challenging due to cryptic 
      biosynthetic gene clusters, low titers, and arduous purifications. Herein, we 
      describe SNaPP (Synthetic Natural Product Inspired Cyclic Peptides), a method for 
      identifying NP-inspired bioactive peptides. SNaPP expedites bioactive molecule 
      discovery by combining bioinformatics predictions of nonribosomal peptide 
      synthetases with chemical synthesis of the predicted natural products (pNPs). 
      SNaPP utilizes a recently discovered cyclase, the penicillin binding protein-like 
      cyclase, as the lynchpin for the development of a library of head-to-tail cyclic 
      peptide pNPs. Analysis of 500 biosynthetic gene clusters allowed for 
      identification of 131 novel pNPs. Fifty-one diverse pNPs were synthesized using 
      solid phase peptide synthesis and solution-phase cyclization. Antibacterial 
      testing revealed 14 pNPs with antibiotic activity, including activity against 
      multidrug-resistant Gram-negative bacteria. Overall, SNaPP demonstrates the power 
      of combining bioinformatics predictions with chemical synthesis to accelerate the 
      discovery of bioactive molecules.
FAU - Hostetler, Matthew A
AU  - Hostetler MA
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Smith, Chloe
AU  - Smith C
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Nelson, Samantha
AU  - Nelson S
AD  - Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 
      West Lafayette, Indiana 47907, United States.
FAU - Budimir, Zachary
AU  - Budimir Z
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Modi, Ramya
AU  - Modi R
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Woolsey, Ian
AU  - Woolsey I
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Frerk, Autumn
AU  - Frerk A
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Baker, Braden
AU  - Baker B
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Gantt, Jessica
AU  - Gantt J
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
FAU - Parkinson, Elizabeth I
AU  - Parkinson EI
AUID- ORCID: 0000-0002-3665-5522
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United 
      States.
AD  - Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 
      West Lafayette, Indiana 47907, United States.
LA  - eng
GR  - P30 CA023168/CA/NCI NIH HHS/United States
GR  - R35 GM138002/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - United States
TA  - ACS Chem Biol
JT  - ACS chemical biology
JID - 101282906
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Biological Products)
RN  - 0 (Penicillin-Binding Proteins)
RN  - 0 (Peptides, Cyclic)
SB  - IM
MH  - Anti-Bacterial Agents/chemistry/pharmacology
MH  - Biological Products/*chemistry
MH  - Computational Biology
MH  - Cyclization
MH  - Drug Discovery
MH  - Drug Resistance, Multiple, Bacterial/drug effects
MH  - Microbial Sensitivity Tests
MH  - Multigene Family
MH  - Penicillin-Binding Proteins/chemistry
MH  - Peptides, Cyclic/*chemistry
MH  - Solid-Phase Synthesis Techniques
PMC - PMC8610019
COIS- The authors declare no competing financial interest.
EDAT- 2021/10/27 06:00
MHDA- 2022/02/01 06:00
PMCR- 2022/10/26
CRDT- 2021/10/26 17:14
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/10/26 17:14 [entrez]
PHST- 2022/10/26 00:00 [pmc-release]
AID - 10.1021/acschembio.1c00641 [doi]
PST - ppublish
SO  - ACS Chem Biol. 2021 Nov 19;16(11):2604-2611. doi: 10.1021/acschembio.1c00641. 
      Epub 2021 Oct 26.