CSIRO PUBLISHING | Australian Journal of Chemistry

This collection honours the eminent peptide chemist, Professor David J. Craik, from the Institute for Molecular Bioscience, The University of Queensland, Australia, on the occasion of his 70th birthday. David’s many friends and colleagues have marked the splendid milestone of his reaching 70 years of age by contributing to this Special Issue of Australian Journal of Chemistry.

Prof. Craik discovered the cyclotide family of circular proteins and has characterised the structures of many animal toxins, including conotoxins from cone snail venoms. His research team focuses on applications of circular proteins, drugs in plants, toxins and NMR in drug design. He is author of over 800 scientific papers. He is a Fellow of the Royal Society and of the Australian Academy of Science, and an Officer (AO) of the Order of Australia. He has received numerous awards and is also Director of the ARC Centre of Excellence in Peptide and Protein Science (CIPPS).

This collection contains papers representing state-of-the-art investigations into peptide and protein science.

Guest Editors
Prof. Ed Nice (Monash University), Prof. Mibel Aguilar (Monash University) & Prof. John Wade (The Florey)

Last Updated: 20 Oct 2025

CH25047The potential of classical antibacterial peptides in mammalian antiviral chemotherapy

Laszlo Otvos

An illustration posing the question, “Can classical antibacterial peptides be used for anti-virus therapy?”

The potential of classical antimicrobial peptides in anti-virus therapy is discussed in light of research spanning decades. Neither the in vitro activity nor the in vivo efficacy results are strongly encouraging for continuous clinical development. (Image credit: Laszlo Otvos.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25108Inheritance and covariation of specialised metabolites among cannabis chemotypes

Matthew T. Welling

, Myrna A. Deseo

, Laura Steel, Gayathree I. Senevirathne

, Kim L. Johnson, Anthony R. Gendall, Monika S. Doblin and Antony Bacic

Graph showing segregation of F2 plants into chemotypes I, II and III.

A genetically female Δ⁹-THC-type chemotype I plant was crossed with a genetically female CBD-type chemotype III plant. The resulting Δ⁹-THC and CBD intermediate chemotype II F₁ plant was selfed and the inflorescences of seed-propagated F₂ plants were analysed by ultra-high-performance liquid chromatography–electrospray ionisation–high-resolution mass spectrometry using data-dependent MS² acquisition. A plot of the Δ⁹-THC_tot and CBD_tot contents and principal component analysis showed the distinct segregation of F₂ plants into chemotypes I, II and III. (Image credit: M. T. Welling and M. A. Deseo.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25081Electrophilic fragment screening using native mass spectrometry to identify covalent probes for surface cysteines

Jack W. Klose

, Yezhou Yu

, Giovanna Di Trapani

, Kathryn F. Tonissen

, Louise M. Sternicki

and Sally-Ann Poulsen

Schematic of surface exposed cysteine residues of carbonic anhydrase III and a spectrum of native mass spectrometry peaks.

Native mass spectrometry (nMS) was applied to screen an electrophilic covalent fragment library to identify ligands for the surface exposed cysteine residues of a soluble protein (carbonic anhydrase III), to determine which cysteines were modified and to measure the simultaneous binding of an orthosteric noncovalent inhibitor and covalent fragment hit. (Image credit: S.-A. Poulsen and L. M. Sternicki.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25086Rational design and selection of next-generation cyclotide drugs using the knotted cyclic peptide scaffold MCoTI-II

Sven Ullrich

, Grégoire Jean-Baptiste Philippe

, Choi Yi Li

and Hiroaki Suga

Schematic showing the solution structure of MCoTI-II with cystine-knotted disulfide bridges highlighted.

This mini-review highlights tactics to engineer MCoTI-II, a cyclic cystine-knot peptide natural product, into next-generation therapeutics and diagnostics. Through both rational modification and genetically encoded selection platforms, variants of the MCoTI-II cyclotide have been developed for a diverse range of potential biomedical applications. (Image credit: Sven Ullrich.)

This article belongs to the collection: 70th Birthday tribute to Prof. David Craik.

CH25093Effect of histidine on the antimicrobial peptide maculatin 1.1 solution-state NMR and molecular dynamics simulation structures at different protonation states

Marc-Antoine Sani

, David W. Keizer

and Frances Separovic

Graphic of the lowest energy refined structures of M2 in DPC micelles at pH 5 and 7 in buffer and exposed to water.

The solution structure and topology of a pH-sensitive, histidine-rich analogue of the antimicrobial peptide maculatin 1.1 were investigated using circular dichroism, solution-state NMR spectroscopy and molecular dynamics simulations. The peptide conformation transitioned from unstructured in buffer to a straight water-exposed or more buried bent α-helix in DPC micelles at pH 5 or 7 respectively. (Image credit: Marc-Antoine Sani.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25059The development of a bioassay expressing the human MRGPRX2 receptor for ex vivo drug discovery

Jan Tytgat

Illustration of the action of a venom on MRGPRX2. The GIRK1/2 channel opens, generating a flow of inward K current.

Mast cells of our immune system are generally difficult and expensive to maintain in vitro and, therefore, not economical to use in drug discovery. The development of a bioassay expressing the human mas-related G protein-coupled receptor-X2 receptor linked to potassium channels in a host cell offers a good alternative. (Image credit: Jan Tytgat.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25091Addressing antimicrobial resistance by using macrocyclic peptides

Samilla B. Rezende

, Elizabete S. Cândido

, Ludovico Migliolo

, Marlon H. Cardoso

and Octávio L. Franco

An illustration showing the pathway to antimicrobial drug development through the use of macrocyclic peptides and AI.

Macrocyclic peptides present cyclic scaffolds, disulfide bonds and constrained arrangements, providing structural stability and diverse antimicrobial mechanisms. Through computational refinement, optimal sequences can be designed to enhance selectivity, stability and therapeutic potential. These advances accelerate drug development, enabling next-generation, peptide-based therapeutics to effectively combat antimicrobial resistance. (Image credit: S. B. Rezende et al.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25100Ribosomally synthesised and post-translationally modified peptides (RiPPs) from marine demosponges and their microsymbionts

Lakmini Kosgahakumbura, Jayani Gamage

, Chamari M. Hettiarachchi, Paco Cárdenas and Sunithi Gunasekera

An image of ribosomally synthesised and post-translationally modified peptides from marine sponges and microbes.

This review highlights ribosomally synthesised and post-translationally modified peptides (RiPPs) from sponges and their microsymbionts. It covers sponge-derived RiPPs, including asteropine A, asteropsins, barrettides, aculeines, stylissamides, recifin A, neopetrosiamides and halichondamide A, as well as RiPPs isolated from sponge microsymbionts, such as polytheonamides, lanthipeptides and thiopeptides. Finally, the review summarises current analytical and genomic tools for RiPP identification and emphasises future perspectives for exploring their ecological and pharmaceutical potential. (Image credit: Sunithi Gunasekera, Jayani Gamage and Paco Cárdenas.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25124One-pot iterative native chemical ligation–desulfurisation chemistry leveraging a coumarin-based photolabile protecting group for cysteine

Lucas Kambanis, Timothy S. Chisholm, Peter H. G. Egelund, Sameer S. Kulkarni and Richard J. Payne

A graphic showing the one-pot iterative ligation–desulfurisation method using 7-diethylamino-3-methyl coumarin.

This communication reports an iterative one-pot native chemical ligation–desulfurisation method using 7-diethylamino-3-methyl coumarin (DEAMC) as a cysteine protecting group. Selective desulfurisation is conducted in the presence of DEAMC-protected cysteine, enabling subsequent photodeprotection and ligation without purification. The utility of this strategy was demonstrated by the efficient one-pot synthesis of a 60-residue mucin-1 peptide. (Image credit: Lucas Kambanis.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25080Liver microsome stability of N-methylated cyclic hexapeptides is decreased by the presence of cis-amide bonds

Huy N. Hoang, David P. Fairlie and Timothy A. Hill

A bar graph with chemical diagrams showing the relative liver microsomal clearance of stable and unstable N-methylated cyclic hexapeptides.

Hepatic stability is crucial for achieving oral bioavailability, as drugs rapidly metabolised by the liver fail to reach effective blood concentrations. This study evaluated the rat liver microsomal stability of N-methylated cyclic hexapeptides. Despite similar sequences, large differences in stability emerged. Poor stability correlated strongly with the presence of cis-amide bonds. NMR and modelling confirmed that cis geometry exposes N-methyl groups to enzymatic attack. These findings identify a cis-amide bond as a key metabolic liability in cyclic peptide drug design. (Image credit: Huy Hoang and Timothy Hill.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25082A peptide journey through the scientific discoveries of David Craik – a personal reflection

Christian W. Gruber

Photograph of David Craik on a field trip, navigating the team through the mist.

This article reflects on the groundbreaking contributions of Professor David Craik to peptide science. His discovery and characterisation of cyclotides – circular plant peptides tied together by a cystine knot – reshaped our understanding of protein stability and inspired new ways to design medicines. From uncovering the enzymes behind peptide cyclisation to pioneering plant-based production of drugs, David’s work bridges structural biology, biodiversity and translational science, leaving a lasting impact on both fundamental research and practical applications. (Photograph by Christian Gruber.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.

CH25071Proline hydroxylation and C-terminal amidation in µ-conotoxins increase structural stability and potency at sodium channels

Victoria A. Adegoke, Yashad Dongol, Tye Gonzalez, Angela Song, Richard J. Clark, Richard J. Lewis

, Anne C. Conibear

and K. Johan Rosengren

Diagram showing the various structure and function assays used to study conotoxin posttranslational modifications.

Conotoxins serve as useful model peptides to understand the effects of protein posttranslational modifications (PTMs). Here, we focus on proline hydroxylation and C-terminal amidation of conotoxins PIIIA and TIIIA. Structure and function assays highlight distinct roles of these PTMs in oxidative folding, structural integrity and activity at sodium channels, advancing our understanding of PTM function in conotoxin pharmacology. (Image credit: Anne C. Conibear.)

This article belongs to the collection: 70th Birthday tribute to Professor David Craik.