RESUMO
There are still no linear antimicrobial peptides (AMPs) available as a treatment option against bacterial infections. This is caused by several drawbacks that come with AMPs such as limited proteolytic stability and low selectivity against human cells. In this work, we screened a small library of rationally designed new peptides based on the cell-penetrating peptide sC18* toward their antimicrobial activity. We identified several effective novel AMPs and chose one out of this group to further increase its potency. Therefore, we introduced a triazole bridge at different positions to provide a preformed helical structure, assuming that this modification would improve (i) proteolytic stability and (ii) membrane activity. Indeed, placing the triazole bridge within the hydrophilic part of the linear analogue highly increased membrane activity as well as stability against enzymatic digestion. The new peptides, 8A and 8B, demonstrated high activity against several bacterial species tested including pathogenic N. gonorrhoeae and methicillin-resistant S. aureus. Since they exhibited significantly good tolerability against human fibroblast and blood cells, these novel peptides offer true alternatives for future clinical applications and are worth studying in more detail.
Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Triazóis , Humanos , Triazóis/farmacologia , Triazóis/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/síntese química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Neisseria gonorrhoeae/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Fibroblastos/efeitos dos fármacosRESUMO
Cell-penetrating peptides (CPPs) have been explored as versatile tools to transport various molecules into cells. The uptake mechanism of CPPs is still not clearly understood and most probably depends on several factors like the nature of the CPP itself, the attached cargo, the investigated cell system, and other experimental conditions, such as temperature and concentration. One of the first steps of internalization involves the interaction of CPPs with negatively charged molecules present at the outer layer of the cell membrane. Recently, thiol-mediated uptake has been found to support the effective translocation of sulfhydryl-bearing substances that would actually not be cell-permeable. Within this work, we aimed to understand the relevance of thiol reactivity for the uptake mechanism of cysteine-containing CPPs that we have developed previously in our group. Therefore, we compared the two peptides, sC18-Cys and CaaX-1, in their single reduced and dimeric disulfide versions. Cytotoxicity, intracellular accumulation, and impact on the internalization process of the disulfides were investigated in HeLa cells. Both disulfide CPPs demonstrated significantly stronger cytotoxic effects and membrane activity compared with their reduced counterparts. Notably, thiol-mediated uptake could be excluded as a main driver for translocation, showing that peptides like CaaX-1 are most likely taken up by other mechanisms.
Assuntos
Peptídeos Penetradores de Células , Dissulfetos , Compostos de Sulfidrila , Humanos , Dissulfetos/química , Dissulfetos/metabolismo , Células HeLa , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
Assuntos
Cicatriz , Colágeno , Fibroblastos , Cicatrização , Peixe-Zebra , Humanos , Animais , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Colágeno/metabolismo , Cicatrização/efeitos dos fármacos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/tratamento farmacológico , Pele/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Fibrose , Peptídeos/farmacologia , Peptídeos/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacosRESUMO
Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their sequences, inserting a triple-glycine linker, adding an N-terminal tryptophan residue, and generating a D-amino acid variant, resulting in the generation of seven new peptides. We investigated their antimicrobial activity against gram-positive and gram-negative bacteria, their cytotoxicity to murine cells, and the biostability of the modified peptides in serum. We identified a novel antimicrobial peptide, WRK-30, with enhanced antimicrobial potency against S. aureus and MRSA. Additionally, WRK-30 was less cytotoxic to eukaryotic cells, allowing its application in higher concentrations in an in vivo setting. In conclusion, we identified a novel CLEC3A-derived antimicrobial peptide WRK-30 with significantly improved therapeutic properties and the potential to widen the repertoire of conventional antibiotics.
RESUMO
Personal medicine aims to provide tailor-made diagnostics and treatments and has been emerged as a promising but challenging strategy during the last years. This includes the active delivery and localization of a therapeutic compound to a targeted site of action within a cell. An example being targeting the interference of a distinct protein-protein interaction (PPI) within the cell nucleus, mitochondria or other subcellular location. Therefore, not only the cell membrane has to be overcome but also the final intracellular destination has to be reached. One approach which fulfills both requirements is to use short peptide sequences that are able to translocate into cells as targeting and delivery vehicles. In fact, recent progress in this field demonstrates how these tools can modulate the pharmacological parameters of a drug without compromising its biological activity. Beside classical targets that are addressed by various small molecule drugs such as receptors, enzymes, or ion channels, PPIs have received increasing attention as potential therapeutic targets. Within this review, we will provide a recent update on cell-permeable peptides targeting subcellular destinations. We include chimeric peptide probes that combine cell-penetrating peptides (CPPs) and a targeting sequence, as well peptides having intrinsic cell-permeability and which are often used to target PPIs.
Assuntos
Peptídeos Penetradores de Células , Mitocôndrias , Membrana CelularRESUMO
Bacterial biofilm formation remains a serious problem for clinical materials and often leads to implant failure. To counteract bacterial adhesion, which initiates biofilm formation, the development of antibiotic surface coating strategies is of high demand and warrants further investigations. In this study, we have created bifunctional chimeric peptides by fusing the recently developed antimicrobial peptide MGD2 (GLRKRLRKFFNKIKF) with different titanium-binding sequences. The novel peptides were investigated regarding their antibacterial potential against a set of different bacterial strains including drug-resistant Staphylococcus aureus. All peptides showed high antimicrobial activities both when in solution and when immobilized on titanium surfaces. Owing to the ease of synthesis and handling, the herein described peptides might be a true alternative to prevent bacterial biofilm formation.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Titânio/farmacologia , Peptídeos/farmacologia , Antibacterianos/farmacologia , Propriedades de Superfície , Biofilmes , Materiais Revestidos BiocompatíveisRESUMO
Herein, the design and synthesis of peptide-drug conjugates (PDCs) including different variants of the cell-penetrating peptide sC18 is presented. We first generated a series of novel sequence mutants of sC18 having either amino acid deletions and/or substitutions, and then tested their biological activity. The effects of histidine substituents were found to be not meaningful for sC18 uptake and cell selectivity. Moreover, building a nearly perfect amphipathic structure within a shortened sC18 derivative provided a peptide that was highly membrane-active, but also too cytotoxic. As a result, the most promising analog was sC18ΔE, which stands out due to its higher uptake efficacy compared to parent sC18. In the last set of experiments, we let the peptides react with the cytotoxic drug doxorubicin by Thiol-Michael addition to form novel PDCs. Our results indicate that sC18ΔE could be a more efficient drug carrier than parent sC18 for biomedical applications. However, cellular uptake using endocytosis and resulting entrapment of cargo inside vesicles is still a major critical step to overcome in CPP-containing peptide-drug development.
Assuntos
Antineoplásicos , Peptídeos Penetradores de Células , Antineoplásicos/farmacologia , Peptídeos Penetradores de Células/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Histidina , Compostos de SulfidrilaRESUMO
The replication of human cytomegalovirus (HCMV) involves a process termed nuclear egress, which enables translocation of newly formed viral capsids from the nucleus into the cytoplasm. The HCMV core nuclear egress complex (core NEC), a heterodimer of viral proteins pUL50 and pUL53, is therefore considered a promising target for new antiviral drugs. We have recently shown that a 29-mer peptide presenting an N-terminal alpha-helical hook-like segment of pUL53, through which pUL53 interacts with pUL50, binds to pUL50 with high affinity, and inhibits the pUL50-pUL53 interaction in vitro. Here, we show that this peptide is also able to interfere with HCMV infection of cells, as well as with core NEC formation in HCMV-infected cells. As the target of the peptide, i.e., the pUL50-pUL53 interaction, is localized at the inner nuclear membrane of the cell, the peptide had to be equipped with translocation moieties that facilitate peptide uptake into the cell and the nucleus, respectively. For the resulting fusion peptide (NLS-CPP-Hook), specific cellular and nuclear uptake into HFF cells, as well as inhibition of infection with HCMV, could be demonstrated, further substantiating the HCMV core NEC as a potential antiviral target.
RESUMO
The mitochondrial intermembrane space protein AIFM1 has been reported to mediate the import of MIA40/CHCHD4, which forms the import receptor in the mitochondrial disulfide relay. Here, we demonstrate that AIFM1 and MIA40/CHCHD4 cooperate beyond this MIA40/CHCHD4 import. We show that AIFM1 and MIA40/CHCHD4 form a stable long-lived complex in vitro, in different cell lines, and in tissues. In HEK293 cells lacking AIFM1, levels of MIA40 are unchanged, but the protein is present in the monomeric form. Monomeric MIA40 neither efficiently interacts with nor mediates the import of specific substrates. The import defect is especially severe for NDUFS5, a subunit of complex I of the respiratory chain. As a consequence, NDUFS5 accumulates in the cytosol and undergoes rapid proteasomal degradation. Lack of mitochondrial NDUFS5 in turn results in stalling of complex I assembly. Collectively, we demonstrate that AIFM1 serves two overlapping functions: importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay that ensures efficient interaction of MIA40/CHCHD4 with specific substrates.
Assuntos
Fator de Indução de Apoptose , Complexo I de Transporte de Elétrons , Proteínas de Transporte da Membrana Mitocondrial , Fator de Indução de Apoptose/metabolismo , Dissulfetos/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Células HEK293 , Humanos , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Oxirredução , Transporte ProteicoRESUMO
During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-helix motif of human angiotensin-converting enzymeâ 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of α1, a series of peptides, N-capped with either Ac-ßHAsp-[ProM-5] or Ac-ßHAsp-PP, were prepared and their α-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the α-helical content and, noteworthy, led to the identification of an Ac-ßHAsp-PP-capped peptide displaying a very strong binding affinity (KD =62â nM).
Assuntos
Enzima de Conversão de Angiotensina 2 , Tratamento Farmacológico da COVID-19 , Humanos , Peptídeos/química , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
The human gonadotropin releasing hormone (GnRH-I) and its sea lamprey analogue GnRH-III specifically bind to GnRH receptors on cancer cells and can be used as targeting moieties for targeted tumor therapy. Considering that the selective release of drugs in cancer cells is of high relevance, we were encouraged to develop cleavable, self-immolative GnRH-III-drug conjugates which consist of a p-aminobenzyloxycarbonlyl (PABC) spacer between a cathepsin B-cleavable dipeptide (Val-Ala, Val-Cit) and the classical anticancer drugs daunorubicin (Dau) and paclitaxel (PTX). Alongside these compounds, non-cleavable GnRH-III-drug conjugates were also synthesized, and all compounds were analyzed for their antiproliferative activity. The cleavable GnRH-III bioconjugates revealed a growth inhibitory effect on GnRH receptor-expressing A2780 ovarian cancer cells, while their activity was reduced on Panc-1 pancreatic cancer cells exhibiting a lower GnRH receptor level. Moreover, the antiproliferative activity of the non-cleavable counterparts was strongly reduced. Additionally, the efficient cleavage of the Val-Ala linker and the subsequent release of the drugs could be verified by lysosomal degradation studies, while radioligand binding studies ensured that the GnRH-III-drug conjugates bound to the GnRH receptor with high affinity. Our results underline the high value of GnRH-III-based homing devices and the application of cathepsin B-cleavable linker systems for the development of small molecule drug conjugates (SMDCs).
Assuntos
Hormônio Liberador de Gonadotropina , Terapia de Alvo Molecular , Neoplasias Ovarianas , Receptores LHRH , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Catepsina B/química , Catepsina B/uso terapêutico , Linhagem Celular Tumoral , Daunorrubicina/química , Daunorrubicina/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Terapia de Alvo Molecular/métodos , Paclitaxel/química , Paclitaxel/uso terapêutico , Petromyzon , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/uso terapêutico , Receptores LHRH/uso terapêuticoRESUMO
The surface decoration of nanoparticles with cell-penetrating peptides (CPPs) represents a common technique for intracellular delivery of nanotherapeutics. Conjugate formation can be performed via covalent or non-covalent strategies. Here, we describe on the synthesis of silica nanoparticles, a well-known inorganic drug delivery vehicle type, and their surface modification with cell-penetrating peptides using sC18 and derivatives thereof. Moreover, physicochemical as well as biological characterization methods, including cellular uptake measurements, of particle-peptide conjugates are described.
Assuntos
Nanopartículas , Peptídeos Penetradores de Células , Sistemas de Liberação de Medicamentos , Dióxido de SilícioRESUMO
Cell-penetrating peptides (CPPs) are versatile tools to deliver various molecules into different cell types. The majority of CPPs are usually represented by linear structures, but numerous recent studies demonstrated cyclization to be an effective strategy leading to favorable biological activities. Here we describe two different methods for the side chain and backbone cyclization of CPPs . Furthermore, we highlight straightforward procedures for the covalent coupling of fluorophores or cytotoxic payloads.
Assuntos
Peptídeos Penetradores de Células/metabolismo , CiclizaçãoRESUMO
CK2α and CK2α' are paralogous catalytic subunits of CK2, which belongs to the eukaryotic protein kinases. CK2 promotes tumorigenesis and the spread of pathogenic viruses like SARS-CoV-2 and is thus an attractive drug target. Efforts to develop selective CK2 inhibitors binding offside the ATP site had disclosed the αD pocket in CK2α; its occupation requires large conformational adaptations of the helix αD. As shown here, the αD pocket is accessible also in CK2α', where the necessary structural plasticity can be triggered with suitable ligands even in the crystalline state. A CK2α' structure with an ATP site and an αD pocket ligand guided the design of the bivalent CK2 inhibitor KN2. It binds to CK2 with low nanomolar affinity, is cell-permeable, and suppresses the intracellular phosphorylation of typical CK2 substrates. Kinase profiling revealed a high selectivity of KN2 for CK2 and emphasizes the selectivity-promoting potential of the αD pocket.
Assuntos
Caseína Quinase II/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Trifosfato de Adenosina/metabolismo , Caseína Quinase II/química , Caseína Quinase II/metabolismo , Cristalização , Células HEK293 , Células HeLa , Humanos , Ligantes , Fosforilação , Conformação Proteica , Especificidade por SubstratoRESUMO
Cell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane is a hallmark and supports optimal lipid-peptide interactions. Incorporation of hydrophobic moieties, such as carboranes (CBs), has the potential to increase the lipophilicity of peptides, and thus, to facilitate the formation of secondary structures. Herein, we present synthesis and biophysical as well as biological characterization of carborane-CPP conjugates having incorporated one or more CB clusters. Our results highlight the possibility to modulate the secondary structure of CPPs by the addition of CB's leading to constructs with altered membrane activity and promising use in terms of nucleic acid delivery.
RESUMO
Biofilm formation and inflammations are number one reasons of implant failure and cause a severe number of postoperative complications every year. To functionalize implant surfaces with antibiotic agents provides perspectives to minimize and/or prevent bacterial adhesion and proliferation. In recent years, antimicrobial peptides (AMP) have been evolved as promising alternatives to commonly used antibiotics, and have been seen as potent candidates for antimicrobial surface coatings. This review aims to summarize recent developments in this field and to highlight examples of the most common techniques used for preparing such AMP-based medical devices. We will report on three different ways to pursue peptide coatings, using either binding sequences (primary approach), linker layers (secondary approach), or loading in matrixes which offer a defined release (tertiary approach). All of them will be discussed in the light of current research in this area.
Assuntos
Peptídeos Antimicrobianos/farmacologia , Bactérias/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Próteses e Implantes , Propriedades de Superfície/efeitos dos fármacosRESUMO
The antimicrobial protein CAP18 (approximate molecular weight: 18â¯000), which was first isolated from rabbit granulocytes, comprises a C-terminal fragment that has negatively charged lipopolysaccharide binding activity. In this study, we found that CAP18 (106-121)-derived (sC18)2 peptides have macropinocytosis-inducible biological functions. In addition, we found that these peptides are highly applicable for use as extracellular vesicle (exosomes, EV)-based intracellular delivery, which is expected to be a next-generation drug delivery carrier. Here, we demonstrate that dimerized (sC18)2 peptides can be easily introduced on EV membranes when modified with a hydrophobic moiety, and that they show high potential for enhanced cellular uptake of EVs. By glycosaminoglycan-dependent induction of macropinocytosis, cellular EV uptake in targeted cells was strongly increased by the peptide modification made to EVs, and intriguingly, our herein presented technique is efficiently applicable for the cytosolic delivery of the biologically cell-killing functional toxin protein, saporin, which was artificially encapsulated in the EVs by electroporation, suggesting a useful technique for EV-based intracellular delivery of biofunctional molecules.
Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Penetradores de Células/química , Sistemas de Liberação de Medicamentos/métodos , Exossomos/química , Saporinas/administração & dosagem , Animais , Células CHO , Cricetulus , Composição de Medicamentos/métodos , Células HeLa , Humanos , Células MCF-7 , CatelicidinasRESUMO
This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)-drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP-drug conjugate.
Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/síntese química , Citostáticos/administração & dosagem , Citostáticos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Citostáticos/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/tendências , Humanos , Estrutura Molecular , Fenômenos de Química OrgânicaRESUMO
Cysteine prenylation is a post-translational modification that is used by nature to control crucial biological functions of proteins, such as membrane trafficking, signal transduction, and apoptosis. It mainly occurs in eukaryotic proteins at a C-terminal CaaX box and is mediated by prenyltransferases. Since the discovery of prenylated proteins, various tools have been developed to study the mechanisms of prenyltransferases, as well as to visualize and to identify prenylated proteins. Herein, we introduce cell-permeable peptides bearing a C-terminal CaaX motif based on Ras sequences. We demonstrate that intracellular accumulation of those peptides in different cells is controlled by the presence of their CaaX motif and that they specifically interact with intracellular prenyltransferases. As proof of concept, we further highlight their utilization to alter downstream signaling of Ras proteins, particularly of K-Ras-4B, in pancreatic cancer cells. Application of this strategy holds great promise to better understand and regulate post-translational cysteine prenylation.
Assuntos
Alquil e Aril Transferases/genética , Neoplasias/genética , Prenilação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Sequência de Aminoácidos/genética , Cisteína/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Células MCF-7 , Neoplasias/patologia , Peptídeos/genética , Peptídeos/farmacologia , Processamento de Proteína Pós-Traducional/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Three chiral tridentate N^N^S coordinating pyridine-carbaldehyde (S)-N4-(α-methylbenzyl)thiosemicarbazones (HTSCmB) were synthesised along with lysine-modified derivatives. One of them was selected and covalently conjugated to the cell-penetrating peptide sC18 by solid-phase peptide synthesis. The HTSCmB model ligands, the HTSCLp derivatives and the peptide conjugate rapidly and quantitatively form very stable PtII chlorido complexes [Pt(TSC)Cl] when treated with K2 PtCl4 in solution. The Pt(CN) derivatives were obtained from one TSCmB model complex and the peptide conjugate complex through Cl- âCN- exchange. Ligands and complexes were characterised by NMR, IR spectroscopy, HR-ESI-MS and single-crystal XRD. Intriguingly, no decrease in cell viability was observed when testing the biological activity of the lysine-tagged HdpyTSCLp, its sC18 conjugate HdpyTSCL-sC18 or the PtCl and Pt(CN) conjugate complexes in three different cell lines. Thus, given the facile and effective preparation of such Pt-TSC-peptide conjugates, these systems might pave the way for future use in late-stage labelling with Pt radionuclides and application in nuclear medicine.