10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities

Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeu...

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Main Authors: Su-Jin Kim, Tae-Bong Kang, Dong-Hyuk Kim, Minho Keum, Sung-Hee Lee, Ji-Hun Kim, Sang-Hyuck Lee, Jihoon Kim, Hyuk-Jung Kweon, Jae-Won Park, Beom-Jun Kim, Hyung-Sik Won
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/11/11/1588
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author Su-Jin Kim
Tae-Bong Kang
Dong-Hyuk Kim
Minho Keum
Sung-Hee Lee
Ji-Hun Kim
Sang-Hyuck Lee
Jihoon Kim
Hyuk-Jung Kweon
Jae-Won Park
Beom-Jun Kim
Hyung-Sik Won
author_facet Su-Jin Kim
Tae-Bong Kang
Dong-Hyuk Kim
Minho Keum
Sung-Hee Lee
Ji-Hun Kim
Sang-Hyuck Lee
Jihoon Kim
Hyuk-Jung Kweon
Jae-Won Park
Beom-Jun Kim
Hyung-Sik Won
author_sort Su-Jin Kim
collection DOAJ
description Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W<sub>2</sub>L<sub>4</sub>K<sub>4</sub> (WALK244.01~WALK244.10) and W<sub>2</sub>L<sub>4</sub>K<sub>3</sub> (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 μg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.
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spelling doaj.art-711c07bf8cab407db2fb0311a2a4cba32023-11-24T03:28:49ZengMDPI AGAntibiotics2079-63822022-11-011111158810.3390/antibiotics1111158810-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory ActivitiesSu-Jin Kim0Tae-Bong Kang1Dong-Hyuk Kim2Minho Keum3Sung-Hee Lee4Ji-Hun Kim5Sang-Hyuck Lee6Jihoon Kim7Hyuk-Jung Kweon8Jae-Won Park9Beom-Jun Kim10Hyung-Sik Won11BK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 28160, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaDepartment of Family Medicine, School of Medicine, Konkuk University, Chungju 27478, KoreaResearch Institute, EYESEL Co., Ltd., Yongin 16950, KoreaResearch Institute, EYESEL Co., Ltd., Yongin 16950, KoreaBK21 Project Team, Department of Applied Life Science, Graduate School, Konkuk University, Chungju 27478, KoreaNatural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W<sub>2</sub>L<sub>4</sub>K<sub>4</sub> (WALK244.01~WALK244.10) and W<sub>2</sub>L<sub>4</sub>K<sub>3</sub> (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 μg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.https://www.mdpi.com/2079-6382/11/11/1588antimicrobial peptideshost defense peptidesde novo designWALK peptidesantibacterial activityanti-inflammatory activity
spellingShingle Su-Jin Kim
Tae-Bong Kang
Dong-Hyuk Kim
Minho Keum
Sung-Hee Lee
Ji-Hun Kim
Sang-Hyuck Lee
Jihoon Kim
Hyuk-Jung Kweon
Jae-Won Park
Beom-Jun Kim
Hyung-Sik Won
10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
Antibiotics
antimicrobial peptides
host defense peptides
de novo design
WALK peptides
antibacterial activity
anti-inflammatory activity
title 10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
title_full 10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
title_fullStr 10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
title_full_unstemmed 10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
title_short 10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities
title_sort 10 mer and 9 mer walk peptides with both antibacterial and anti inflammatory activities
topic antimicrobial peptides
host defense peptides
de novo design
WALK peptides
antibacterial activity
anti-inflammatory activity
url https://www.mdpi.com/2079-6382/11/11/1588
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