The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Gan, Bee‐Ha; Gaynord, Josephine; Rowe, Sam M.; Deingruber, Tomáš; Spring, David R.

doi:10.1039/d0cs00729c

Cited by 247 publications

(221 citation statements)

References 538 publications

(791 reference statements)

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…For these reasons, modifications to AMPs have been developed with the aim to improve antimicrobial potency and stability while at the same time to reduce toxicity and size. This can be done by chemical modifications such as substitution of one or more amino acid residues of the natural AMP template with other L- or D-amino acids, both proteinogenic or non-proteinogenic, as well as N-terminal acetylation, C-terminal amidation, peptide cyclization (usually via disulfide bond formation and more rarely by backbone cyclization), or introduction of unnatural amino acids to synthesize α-peptoids [ 184 ], β-peptoids [ 185 ], β-peptides [ 186 ], peptide/peptoid hybrids [ 187 , 188 , 189 ] and/or functionalized with lipo-amino acids [ 190 ] or with PEG [ 191 ].…”

Section: Halogenated Ampsmentioning

confidence: 99%

Natural and Synthetic Halogenated Amino Acids—Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics

Mardirossian

Rubini

Adamo³

et al. 2021

Molecules

View full text Add to dashboard Cite

The 3D structure and surface characteristics of proteins and peptides are crucial for interactions with receptors or ligands and can be modified to some extent to modulate their biological roles and pharmacological activities. The introduction of halogen atoms on the side-chains of amino acids is a powerful tool for effecting this type of tuning, influencing both the physico-chemical and structural properties of the modified polypeptides, helping to first dissect and then rationally modify features that affect their mode of action. This review provides examples of the influence of different types of halogenation in amino acids that replace native residues in proteins and peptides. Examples of synthetic strategies for obtaining halogenated amino acids are also provided, focusing on some representative compounds and their biological effects. The role of halogenation in native and designed antimicrobial peptides (AMPs) and their mimetics is then discussed. These are in the spotlight for the development of new antimicrobial drugs to counter the rise of antibiotic-resistant pathogens. AMPs represent an interesting model to study the role that natural halogenation has on their mode of action and also to understand how artificially halogenated residues can be used to rationally modify and optimize AMPs for pharmaceutical purposes.

show abstract

Section: Halogenated Ampsmentioning

confidence: 99%

Natural and Synthetic Halogenated Amino Acids—Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics

Mardirossian

Rubini

Adamo³

et al. 2021

Molecules

View full text Add to dashboard Cite

show abstract

“…Protection from cleavage could be also conferred by modifying or protecting vulnerable peptide bonds so that they cannot be easily accessed [ 37 ]. In some cases, such modifications could be applied just to the N - and C -terminus i.e., C -amidation or N -acetylation [ 38 ].…”

Section: Synthetic Antimicrobial Peptidesmentioning

confidence: 99%

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

Vanzolini

Bruschi

Rinaldi

et al. 2022

IJMS

View full text Add to dashboard Cite

Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.

show abstract

“…This view is compatible with all of the observations which we have presented here. A recent review [54] discusses antibacterial peptides, offering several scenarios of how they may attack the bacterial surface. This further supports the view presented here.…”

Section: The Exceptional Antibacterial Efficacy Of Nanoparticle Alloysmentioning

confidence: 99%

A Pragmatic Perspective of the Antibacterial Properties of Metal-Based Nanoparticles

Sacher

Yelon

2021

Nanomaterials

View full text Add to dashboard Cite

A consideration of the antibacterial efficacy of metal-based nanoparticles, from the point of view of their physicochemical properties, suggests that such efficacy arises from the protein coronas that form around them, and that the contents of the coronas depend on the chemical groups found on the nanoparticle surfaces. We offer a new perspective and new insights, making use of our earlier observations of the physicochemical properties of nanoparticle surfaces, to propose that the nanoparticle serves as a mediator for the formation and activation of the protein corona, which attacks the bacterium. That is, the nanoparticle enhances the body’s natural defenses, using proteins present in body fluids.

show abstract

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Abstract: This review discusses the diversity of structure and physicochemical properties of antimicrobial peptides and their derivatives, various chemical synthetic strategies that have been applied in their development, and how this links to their activity.

Cited by 247 publications

References 538 publications

Natural and Synthetic Halogenated Amino Acids—Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics

Natural and Synthetic Halogenated Amino Acids—Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics

Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

A Pragmatic Perspective of the Antibacterial Properties of Metal-Based Nanoparticles

Contact Info

Product

Resources

About