Synthesis, conformation, and immunoreactivity of new carrier molecules based on repeated tuftsin‐like sequence

Mező, Gábor; Kalászi, Adrián; Reményi, Judit; Májer, Zsuzsa; Hilbert, Ágnes; Láng, Orsolya; Kőhidai, László; Barna, K.; Gaál, D.; Hudecz, Ferenc

doi:10.1002/bip.20024

Cited by 37 publications

(49 citation statements)

References 33 publications

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“…Molecular modelling study suggested a flexible structure for oligotuftsins and also demonstrated accessibility of the ε-amino group of each lysine residue [3]. In case of OT14 as new carrier Lys8 and Lys13 were the most accessible out of the five Lys residues to form chemical linkage with antitubercular compound.…”

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 96%

“…The host cell specific delivery of the active compounds could increase the intracellular concentration [2]. In this study macrophage -as main host cell -specific conjugates were synthesised and characterised [2][3][4][5][6].…”

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

“…A group of sequential oligopeptides based on tuftsin has been developed [5]. The synthetic oligotuftsins consist of tandem pentapeptide repeat units [TKPKG] n (n: 2,4,6,8) derived from the canine tuftsin sequence TKPK extended by a C-terminal Gly [3,5]. The canine tuftsin TKPK, where arginine residues is replaced by lysine, that has also basic character has similar biological activities like the human tuftsin TKPR [8].…”

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

“…However, the lysine residue in the sequence of TKPK can offer a new functional group for connection of a biologically active compound. With the addition of a glycine residue to the C-terminal of TKPK racemisation free condensation of the fragments can be achieved to form larger oligomers [3]. These compounds are nontoxic, nonimmunogenic, biodegradable, and exhibit tuftsin-like biological properties, e.g.…”

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

“…2 shows a typical measurement curve. Following the stable baseline (1) liposomes were introduced (2) and after spreading and rupture of liposomes a lipid bilayer was formed (3). Then the bioactive compound was injected and Δf and ΔR showed the interaction of drug or drug-conjugate with lipid bilayer (4) followed by a rinsing with buffer (5).…”

Section: Bilayer Studiesmentioning

confidence: 99%

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Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

Ábrahám

Baranyai²,

Gyulai

et al. 2016

Colloids and Surfaces B: Biointerfaces

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Novel peptide conjugates of two antitubercular drug ca ndidates were s ynthesi s ed a nd cha ra cteri s ed us i ng new tufts i n peptide derivatives (OT14) as carrier moiety. As antitubercular drug ca ndidates two pyridopyrimidine derivatives, TB803 (2-a l lylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) a nd TB820 (4-oxo-2-(pyrroli di n-1-yl )-pyri do[1,2-a ]pyri mi di n-3-ca rba ldehyde) inhibiting vi tal enzyme of Mycobacterium tuberculosis were applied. Membrane affini ty of the compounds TB803 a nd TB820 a nd their peptide conjugates wa s eva l ua ted us i ng experi menta l l i pi d mono -a nd bi l a yer model s . Penetration ability was assessed tensiometrically from La ngmuir monolayer study a nd a pplying quartz crys tal microbalance for the s upported l ipid bilayer (SLB) system. Mi nimal inhibitory concentration (MIC) values remained in a similar micromolar ra nge for both of the conjugates whi l e thei r cel l ul a r upta k e ra te wa s i mproved s i gni fi ca ntl y compa red to the drug ca ndidates. A correlation was found between membrane affinity properties a nd results of in vitro bi ological i nvestiga ti ons . Ana l ysis of physical/structural properties of SLB in contact with bioactive components and vi s ua l i za ti on of the s tructura l cha nge by a tomic-force microscopy (AFM) provi ded i nformation on the type and route of mol ecul a r i ntera cti on of drug cons truction with lipid l ayers. The possible role of electrostatic i nteractions between lipid layer a nd drug ca ndi da tes wa s tes ted in Langmuir-balance experiments using nega ti vel y cha rged l i pi d mi xture (DPPC+DPPG). Es peci a l l y the pepti de conjugates presented i ncreased membrane affinity due to ca tionic cha ra cter of the pepti de s equence s el ected for the conjugate formation. That is supposed to be one reason for the enhanced cellular uptake observed in vitro for MonoMa c6 cel l line. The conjugation of a ntitubercular a gents to a peptidic ca rrier i s a promi s i ng a pproa ch to enha nce membra ne a ffi ni ty, cel l ul a r upta ke ra te a nd in vitro s el ecti vi ty.

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Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 96%

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

Section: Tuberculosis (Tb) Is a Bacterial Infection Mainly Caused By mentioning

confidence: 99%

Section: Bilayer Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

Ábrahám

Baranyai²,

Gyulai

et al. 2016

Colloids and Surfaces B: Biointerfaces

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Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.

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Recent Developments in Drug Delivery for Treatment of Tuberculosis by Targeting Macrophages

Gairola

Benjamin

Weatherston

et al. 2022

Advanced Therapeutics

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Tuberculosis (TB) is among the greatest public health and safety concerns in the 21st century Mycobacterium tuberculosis, which causes TB, infects alveolar macrophages and uses these cells as one of its primary sites of replication. The current TB treatment regimen, which consists of chemotherapy involving a combination of 3-4 antimicrobials for a duration of 6-12 months, is marked with significant side effects, toxicity, and poor compliance. Targeted drug delivery offers a strategy that can overcome many of the problems of current TB treatment by specifically targeting infected macrophages. Recent advances in nanotechnology and material science have opened an avenue to explore drug carriers that actively and passively target macrophages. This approach can increase the drug penetration into macrophages by using ligands on the nanocarrier that interact with specific receptors for macrophages. This review encompasses the recent development of drug carriers specifically targeting macrophages actively and passively. Future directions and challenges associated with development of effective TB treatment are also discussed.

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Synthesis, conformation, and immunoreactivity of new carrier molecules based on repeated tuftsin‐like sequence

Cited by 37 publications

References 33 publications

Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Recent Developments in Drug Delivery for Treatment of Tuberculosis by Targeting Macrophages

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