Antimicrobial peptide LyeTx I mn∆K labeled with Ga is a potential PET radiopharmaceutical for molecular imaging of infections.

Background: Antimicrobial peptides have been radiolabeled and investigated as molecular diagnostic probes due to their propensity to accumulate in infectious sites rather than aseptic inflammatory lesions. LyeTx I is a cationic peptide from the venom of Lycosa erythrognatha, exhibiting significant antimicrobial activity. LyeTx I mn∆K is a shortened derivative of LyeTx I, with an optimized balance between antimicrobial and hemolytic activities.

EGFR- and Integrin αβ-Targeting Peptides as Potential Radiometal-Labeled Radiopharmaceuticals for Cancer Theranostics.

The burgeoning field of cancer theranostics has witnessed advancements through the development of targeted molecular agents, particularly peptides. These agents exploit the overexpression or mutations of specific receptors, such as the Epidermal Growth Factor receptor (EGFR) and αβ integrin, which are pivotal in tumor growth, angiogenesis, and metastasis. Despite the extensive research into and promising outcomes associated with antibody-based therapies, peptides offer a compelling alternative due to their smaller size, ease of modification, and rapid bioavailability, factors which potentially enhance tumor penetration and reduce systemic toxicity.

Radiosynthesis Standardization and Preclinical Assessment of the [Ga]Ga-DOTA-Ubiquicidin: A Translational Study Targeting Differential Diagnosis of Infectious Processes.

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies.

Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive Tc-labeling for SPECT imaging and radioguided surgery in prostate cancer.

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with Tc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [Tc]Tc-PSMA-I&S obtained by the cold kit.

Comparative Evaluation of Radiochemical and Biological Properties of I- and [Tc]Tc(CO)-Labeled RGD Analogues Planned to Interact with the αβ Integrin Expressed in Glioblastoma.

Radiolabeled peptides with high specificity for overexpressed receptors in tumor cells hold great promise for diagnostic and therapeutic applications. In this work, we aimed at comparing the radiolabeling efficiency and biological properties of two different RGD analogs: GRGDYV and GRGDHV, labeled with iodine-131 (I) and technetium-99m-tricarbonyl complex [Tc][Tc(CO)]. Additionally, we evaluated their interaction with the αβ integrin molecule, overexpressed in a wide variety of tumors, including glioblastoma.

Standardization of the [Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies.

Radiochemical and biological properties of peptides designed to interact with EGF receptor: Relevance for glioblastoma.

Radiolabeled peptides with high specificity to receptors expressed on tumor cells hold a great promise as diagnostic and therapeutic tracers. The main objective of this study was to evaluate the radiochemical and biological properties of two [I]I-peptides, as well as their interaction with the epidermal growth factor receptor (EGFR), overexpressed in a wide variety of tumors, including glioblastoma. The EEEEYFELV peptide and its analogue DEDEYFELV, both designed to interact with EGFR, were chemically synthesized, purified and radiolabeled with iodine-131 ([I]NaI).

Comparative Study of Two Oxidizing Agents, Chloramine T and Iodo-Gen, for the Radiolabeling of β-CIT with Iodine-131: Relevance for Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the , leading to alteration of the integrity of dopaminergic transporters (DATs). In recent years, some radiopharmaceuticals have been used in the clinic to evaluate the integrity of DATs. These include tropane derivatives such as radiolabeled β-CIT and FP-CIT with iodine-123 (I), and TRODAT-1 with metastable technetium-99 (Tc).

Fragments of the second transmembrane helix of three G-protein-coupled receptors: comparative synthetic, structural and conformational studies.

We compared the synthesis and structural/conformational details of the (66-97) segments of the second transmembrane helix of AT1, MAS and B2, all of which belong to the class of G-protein-coupled receptors (GPCR). Step-by-step monitoring of the coupling reactions during the growth of these transmembrane peptides revealed that the increase in the level of difficulty started at the 6-10 regions of the sequence. Possibly due to their long and hydrophobic sequences, the final estimated synthesis yields decreased progressively by up to 20-25%.

Evaluation of Aggregation and Fibril Formation Propensity of Peptides Involved in Amyloid Diseases.

Background: Amyloidosis is defined as a generic term given to a series of proteins/ polypeptides in the form of amyloid fibrils that are deposited in the tissues and give rise to a set of clinical disorders.

Objectives: This work developed an approach to first examine chain association propensities of several amyloidogenic peptides: SNNFGAILSS from the islet amyloid polypeptide (coded IAPP), NAGDVAFV from the protein responsible for corneal amyloidosis (coded Lactoferrin), and (1-42) β-amyloid (coded Amyloid).

Methods: Fmoc-synthesis protocol was applied for the synthesis of IAPP and Lactoferrin whereas Amyloid was synthesized through the Boc-chemistry as early detailed.

Paramagnetic bradykinin analogues as substrates for angiotensin I-converting enzyme: Pharmacological and conformation studies.

This study uses EPR, CD, and fluorescence spectroscopy to examine the structure of bradykinin (BK) analogues attaching the paramagnetic amino acid-type Toac (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) at positions 0, 3, 7, and 9. The data were correlated with the potencies in muscle contractile experiments and the substrate properties towards the angiotensin I-converting enzyme (ACE). A study of the biological activities in guinea pig ileum and rat uterus indicated that only Toac-BK partially maintained its native biological potency among the tested peptides.

Conformational Properties of Seven Toac-Labeled Angiotensin I Analogues Correlate with Their Muscle Contraction Activity and Their Ability to Act as ACE Substrates.

Conformational properties of the angiotensin II precursor, angiotensin I (AngI) and analogues containing the paramagnetic amino acid TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) at positions 0, 1, 3, 5, 8, 9, and 10, were examined by EPR, CD, and fluorescence. The conformational data were correlated to their activity in muscle contraction experiments and to their properties as substrates of the angiotensin I-converting enzyme (ACE). Biological activity studies indicated that TOAC0-AngI and TOAC1-AngI maintained partial potency in guinea pig ileum and rat uterus.

Novel copoly(styrene-divinylbenzene)-resins with different phenylmethylamine groups for use in Peptide synthesis method.

Differently than the 4-methylbenzhydrylamine-resin (MBHAR) which contains a methyl group coupled to the phenylmethylamine-functionalized copoly(styrene-divinilbenzene) structure, alternative resins containing the electron-donating 4-tert-butyl- (BUBHAR) or the electron-withdrawing 2-chloro- (ClBHAR) and 2,4-chloro- (diClBHAR) groups were developed as potential supports for α- carboxamide peptide synthesis. Initially, a time-course investigation of HF cleavage reaction (0 °C) with these resins bearing the vasoconstrictor angiotensin II (AngII, DRVYIHPF) or its Gly(8)-AngII analogue revealed that the peptide- BUBHAR linkage is much more labile than those with ClBHAR or diClBHAR. HF cleavage times of near 2 h or longer than 24 h were needed for complete removal of peptide chains from these two classes of resin, respectively.

Assessment of the aggregation propensity of the β -amyloid peptide during the synthesis and when free in solution.

This work developed an alternative approach targeting the evaluation of the aggregation propensity of the (1-42) β-amyloid peptide (Alzheimer's disease) and some segments, either attached to a polymer during their synthesis or when free in solution. The solvation behavior of peptide-resins was gauged by measuring the swelling of beads in a microscope and the degree of chain motion through EPR spectra of previously labeled resins with an amino acid-type probe. In terms of comparative solvent dissociation power towards aggregated structures, the findings revealed greater values of peptide-resin swelling, peptide chain mobility and solubility when in strong electron donor dimethylsulfoxide than in strong electron acceptor trifluoroethanol.

Short peptide constructs mimic agonist sites of AT(1)R and BK receptors.

Extracellular peptide ligand binding sites, which bind the N-termini of angiotensin II (AngII) and bradykinin (BK) peptides, are located on the N-terminal and extracellular loop 3 regions of the AT(1)R and BKRB(1) or BKRB(2) G-protein-coupled receptors (GPCRs). Here we synthesized peptides P15 and P13 corresponding to these receptor fragments and showed that only constructs in which these peptides were linked by S-S bond, and cyclized by closing the gap between them, could bind agonists. The formation of construct-agonist complexes was revealed by electron paramagnetic resonance spectra and fluorescence measurements of spin labeled biologically active analogs of AngII and BK (Toac(1)-AngII and Toac(0)-BK), where Toac is the amino acid-type paramagnetic and fluorescence quencher 2, 2, 6, 6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid.

Comparative fibril formation of analogs corresponding to the (12-24) segment of the β-amyloid peptide.

The (1-42) β-amyloid peptide is a main component of the plaques found in the brain of patients suffering from the Alzheimer's disease. As the single substitution of Glu for Gln at position 22 of this peptide seems to be responsible for the manifestation of the more severe amyloidosis (Dutch-type), we decided to evaluate the aggregation characteristics of peptide analogs interchanging Glu and Gln residues at positions 22 and also 15 in the minor (12-24) (VHHQ(15)KLVFFAE(22)DV) fragment. The Q15Q22, E15E22, E15Q22 and the native Q15E22 were compared to the (1-42) β-amyloid peptide in terms of fibril or structured aggregates formation propensity.

Application of hyperthermia induced by superparamagnetic iron oxide nanoparticles in glioma treatment.

Gliomas are a group of heterogeneous primary central nervous system (CNS) tumors arising from the glial cells. Malignant gliomas account for a majority of malignant primary CNS tumors and are associated with high morbidity and mortality. Glioblastoma is the most frequent and malignant glioma, and despite the recent advances in diagnosis and new treatment options, its prognosis remains dismal.

Peptides: important tools for the treatment of central nervous system disorders.

This review shows some classical applications of peptides and suggests there is great promise for the treatment of various central nervous system diseases. Actually, peptides are considered the new generation of biologically active tools because they are key regulators in cellular and intercellular physiological responses, which possess enormous potential for the treatment of various diseases. In spite of their clinical potential, native peptides have seen limited use due to their poor bioavailability and low stability in physiological conditions.

Application of electron paramagnetic resonance spectroscopy for validation of the novel (AN+DN) solvent polarity scale.

Based on solvation studies of polymers, the sum (1:1) of the electron acceptor (AN) and electron donor (DN) values of solvents has been proposed as an alternative polarity scale. To test this, the electron paramagnetic resonance isotropic hyperfine splitting constant, a parameter known to be dependent on the polarity/proticity of the medium, was correlated with the (AN+DN) term using three paramagnetic probes. The linear regression coefficient calculated for 15 different solvents was approximately 0.

Functional assessment of angiotensin II and bradykinin analogues containing the paramagnetic amino acid TOAC.

This study characterized pharmacologically the functional responses to agonists angiotensin II (AngII) and bradykinin (BK) derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label at the N-terminal (TOAC1-AngII and TOAC0-BK) and internal (TOAC3-AngII and TOAC3-BK) positions of these vasoactive peptides. Affinity constants of the ligands for AT1 and B2 receptors were evaluated in vitro by binding assays and biological effects by extracellular acidification rates and in vivo by blood pressure responses. In contrast to internally labeled analogues (TOAC3-AngII or TOAC3-BK), the TOAC1-AngII and TOAC0-BK derivatives dose-dependently increased the extracellular acidification rate in adherent cultured Chinese hamster ovary (CHO) cells expressing AT1 or B2 receptors, respectively.

Interpretation of the dissolution of insoluble peptide sequences based on the acid-base properties of the solvent.

The dissolution process of model insoluble peptide sequences was investigated in view of the electron acceptor (AN) and electron donor (DN) solvent properties. The Alzheimer's disease-inducing (1-42) Abeta-amyloid peptide and its (1-21) fragment, the (66-97) transmembrane bradykinin B2 receptor sequence, and the strongly aggregated VVLGAAIV were selected as models of insoluble peptides. Solvents presenting similar AN and DN values failed, despite their polarities, to dissociate peptide chains (free in solution or bound to a polymer).

Polystyrene-type resin used for peptide synthesis: application for anion-exchange and affinity chromatography.

This paper deals with an unusual application for a copolymer of styrene-1% divinylbenzene bearing high amount of aminomethyl groups for anion-exchange and affinity chromatography. The so-called aminomethyl resin (AMR), to date only employed for peptide synthesis, swelled appreciably in water and was used successfully to purify negatively charged peptides. By correlating swelling degree of beads with pH of the media, it was possible to estimate that the AMR amino group pK(a) is approximately 5.